43 results on '"Giugliani, Roberto"'
Search Results
2. Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)
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Geberhiwot, Tarekegn, Wasserstein, Melissa, Wanninayake, Subadra, Bolton, Shaun Christopher, Dardis, Andrea, Lehman, Anna, Lidove, Olivier, Dawson, Charlotte, Giugliani, Roberto, Imrie, Jackie, Hopkin, Justin, Green, James, de Vicente Corbeira, Daniel, Madathil, Shyam, Mengel, Eugen, Ezgü, Fatih, Pettazzoni, Magali, Sjouke, Barbara, Hollak, Carla, Vanier, Marie T., McGovern, Margaret, and Schuchman, Edward
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- 2023
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3. Application of a glycinated bile acid biomarker for diagnosis and assessment of response to treatment in Niemann-pick disease type C1
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Sidhu, Rohini, Kell, Pamela, Dietzen, Dennis J, Farhat, Nicole Y, Do, An Ngoc Dang, Porter, Forbes D, Berry-Kravis, Elizabeth, Reunert, Janine, Marquardt, Thorsten, Giugliani, Roberto, Lourenço, Charles M, Wang, Raymond Y, Movsesyan, Nina, Plummer, Ellen, Schaffer, Jean E, Ory, Daniel S, and Jiang, Xuntian
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Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Neurosciences ,Biotechnology ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Metabolic and endocrine ,2-Hydroxypropyl-beta-cyclodextrin ,Bile Acids and Salts ,Biomarkers ,Female ,Glycine ,Humans ,Intracellular Signaling Peptides and Proteins ,Male ,Niemann-Pick C1 Protein ,Niemann-Pick Disease ,Type C ,Tandem Mass Spectrometry ,Vesicular Transport Proteins ,Bile acid ,N-(3 beta ,5 alpha ,6 beta-trihydroxy-cholan-24-oyl)glycine ,Niemann-Pick disease type C ,diagnosis ,2-hydroxypropyl-beta-cyclodextrin ,treatment assessment ,2-hydroxypropyl-β-cyclodextrin ,N-(3β ,5α ,6β-trihydroxy-cholan-24-oyl)glycine ,Genetics & Heredity ,Genetics ,Clinical sciences - Abstract
Niemann-Pick disease type C (NPC) is a neurodegenerative disease in which mutation of NPC1 or NPC2 gene leads to lysosomal accumulation of unesterified cholesterol and sphingolipids. Diagnosis of NPC disease is challenging due to non-specific early symptoms. Biomarker and genetic tests are used as first-line diagnostic tests for NPC. In this study, we developed a plasma test based on N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine (TCG) that was markedly increased in the plasma of human NPC1 subjects. The test showed sensitivity of 0.9945 and specificity of 0.9982 to differentiate individuals with NPC1 from NPC1 carriers and controls. Compared to other commonly used biomarkers, cholestane-3β,5α,6β-triol (C-triol) and N-palmitoyl-O-phosphocholine (PPCS, also referred to as lysoSM-509), TCG was equally sensitive for identifying NPC1 but more specific. Unlike C-triol and PPCS, TCG showed excellent stability and no spurious generation of marker in the sample preparation or aging of samples. TCG was also elevated in lysosomal acid lipase deficiency (LALD) and acid sphingomyelinase deficiency (ASMD). Plasma TCG was significantly reduced after intravenous (IV) 2-hydroxypropyl-β-cyclodextrin (HPβCD) treatment. These results demonstrate that plasma TCG was superior to C-triol and PPCS as NPC1 diagnostic biomarker and was able to evaluate the peripheral treatment efficacy of IV HPβCD treatment.
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- 2020
4. Application of N-palmitoyl-O-phosphocholineserine for diagnosis and assessment of response to treatment in Niemann-Pick type C disease
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Sidhu, Rohini, Kell, Pamela, Dietzen, Dennis J, Farhat, Nicole Y, Do, An Ngoc Dang, Porter, Forbes D, Berry-Kravis, Elizabeth, Vite, Charles H, Reunert, Janine, Marquardt, Thorsten, Giugliani, Roberto, Lourenço, Charles M, Bodamer, Olaf, Wang, Raymond Y, Plummer, Ellen, Schaffer, Jean E, Ory, Daniel S, and Jiang, Xuntian
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Biotechnology ,Clinical Research ,Neurosciences ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Metabolic and endocrine ,2-Hydroxypropyl-beta-cyclodextrin ,Adolescent ,Adult ,Aged ,Animals ,Biomarkers ,Cats ,Child ,Child ,Preschool ,Chromatography ,Liquid ,Female ,Humans ,Infant ,Infant ,Newborn ,Male ,Middle Aged ,Niemann-Pick Disease ,Type C ,Phosphorylcholine ,Sensitivity and Specificity ,Severity of Illness Index ,Tandem Mass Spectrometry ,Treatment Outcome ,Young Adult ,LysoSM-509 ,N-palmitoyl-O-phosphocholineserine ,Niemann-Pick disease type C ,Diagnosis ,Treatment assessment ,2-Hydroxypropyl-β-cyclodextrin ,Clinical Sciences ,Genetics & Heredity - Abstract
Niemann-Pick type C (NPC) disease is a rare lysosomal storage disorder caused by mutations in either the NPC1 or the NPC2 gene. A new class of lipids, N-acyl-O-phosphocholineserines were recently identified as NPC biomarkers. The most abundant species in this class of lipid, N-palmitoyl-O-phosphocholineserine (PPCS), was evaluated for diagnosis of NPC disease and treatment efficacy assessment with 2-hydroxypropyl-β-cyclodextrin (HPβCD) in NPC. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed and validated to measure PPCS in human plasma and cerebrospinal fluid (CSF). A cutoff of 248 ng/mL in plasma provided a sensitivity of 100.0% and specificity of 96.6% in identifying NPC1 patients from control and NPC1 carrier subjects. PPCS was significantly elevated in CSF from NPC1 patients, and CSF PPCS levels were significantly correlated with NPC neurological disease severity scores. Plasma and CSF PPCS did not change significantly in response to intrathetical (IT) HPβCD treatment. In an intravenous (IV) HPβCD trial, plasma PPCS in all patients was significantly reduced. These results demonstrate that plasma PPCS was able to diagnose NPC1 patients with high sensitivity and specificity, and to evaluate the peripheral treatment efficacy of IV HPβCD treatment.
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- 2020
5. Sanfilippo syndrome: consensus guidelines for clinical care
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Muschol, Nicole, Giugliani, Roberto, Jones, Simon A., Muenzer, Joseph, Smith, Nicholas J. C., Whitley, Chester B., Donnell, Megan, Drake, Elise, Elvidge, Kristina, Melton, Lisa, and O’Neill, Cara
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- 2022
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6. International guidelines for the management and treatment of Morquio A syndrome
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Hendriksz, Christian J, Berger, Kenneth I, Giugliani, Roberto, Harmatz, Paul, Kampmann, Christoph, Mackenzie, William G, Raiman, Julian, Villarreal, Martha Solano, and Savarirayan, Ravi
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Rare Diseases ,Humans ,Internationality ,Mucopolysaccharidosis IV ,Practice Guidelines as Topic ,Radiography ,mucopolysaccharidosis IV ,guidelines ,symptom assessment ,diagnosis ,disease management ,Genetics ,Clinical sciences - Abstract
Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder associated with skeletal and joint abnormalities and significant non-skeletal manifestations including respiratory disease, spinal cord compression, cardiac disease, impaired vision, hearing loss, and dental problems. The clinical presentation, onset, severity and progression rate of clinical manifestations of Morquio A syndrome vary widely between patients. Because of the heterogeneous and progressive nature of the disease, the management of patients with Morquio A syndrome is challenging and requires a multidisciplinary approach, involving an array of specialists. The current paper presents international guidelines for the evaluation, treatment and symptom-based management of Morquio A syndrome. These guidelines were developed during two expert meetings by an international panel of specialists in pediatrics, genetics, orthopedics, pulmonology, cardiology, and anesthesia with extensive experience in managing Morquio A syndrome.
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- 2015
7. Opportunities and challenges for newborn screening and early diagnosis of rare diseases in Latin America.
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Giugliani, Roberto, Taucher, Silvia Castillo, Hafez, Sylvia, Oliveira, Joao Bosco, Rico-Restrepo, Mariana, Rozenfeld, Paula, Zarante, Ignacio, and Gonzaga-Jauregui, Claudia
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NEWBORN screening ,DIAGNOSIS ,RARE diseases ,EARLY diagnosis ,MEDICAL societies - Abstract
Rare diseases (RDs) cause considerable death and disability in Latin America. Still, there is no consensus on their definition across the region. Patients with RDs face a diagnostic odyssey to find a correct diagnosis, which may last many years and creates a burden for caregivers, healthcare systems, and society. These diagnostic delays have repercussions on the health and economic burden created by RDs and continue to represent an unmet medical need. This review analyzes barriers to the widespread adoption of newborn screening (NBS) programs and early diagnostic methods for RDs in Latin America and provides recommendations to achieve this critical objective. Increasing the adoption of NBS programs and promoting early diagnosis of RDs are the first steps to improving health outcomes for patients living with RDs. A coordinated, multistakeholder effort from leaders of patient organizations, government, industry, medical societies, academia, and healthcare services is required to increase the adoption of NBS programs. Patients' best interests should remain the guiding principle for decisions regarding NBS implementation and early diagnosis for RDs. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Diagnosis and Emerging Treatment Strategies for Mucopolysaccharidosis VII (Sly Syndrome).
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de Oliveira Poswar, Fabiano, Nehm, Johanna Henriques, Kubaski, Francyne, Poletto, Edina, and Giugliani, Roberto
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HEMATOPOIETIC stem cell transplantation ,ENZYME replacement therapy ,MUCOPOLYSACCHARIDOSIS ,DIAGNOSIS ,ENZYME deficiency - Abstract
Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an ultra-rare lysosomal disease caused by a deficiency of the enzyme β-glucuronidase (GUS). The diagnosis is suspected based on a range of symptoms that are common to many other MPS types, and it is confirmed through biochemical and molecular studies. Besides supportive treatment, current and emerging treatments include enzyme replacement therapy, hematopoietic stem cell transplantation, and gene therapy. This review summarizes the clinical manifestations, diagnosis, and emerging treatments for MPS VII. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls
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Burton, Barbara K. and Giugliani, Roberto
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- 2012
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10. INITIAL CLINICAL PRESENTATION IN CASES OF INBORN ERRORS OF METABOLISM IN A REFERENCE CHILDREN’S HOSPITAL: STILL A DIAGNOSTIC CHALLENGE
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Romão, Andressa, Simon, Priscila Endlich Alves, Góes, José Eduardo Coutinho, Pinto, Louise Lapagessede Camargo, Giugliani, Roberto, de Luca, Gisele Rozone, and Carvalho, Francisca Ligia Cirilo
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Male ,Adolescent ,Infant, Newborn ,Infant ,Original Articles ,Inborn errors of metabolism ,Hospitals, Pediatric ,Cross-Sectional Studies ,Child, Preschool ,Diagnosis ,Humans ,Female ,Clinical symptoms ,Child ,Referral and Consultation ,Metabolism, Inborn Errors - Abstract
To assess the initial clinical presentation of confirmed cases of inborn errors of metabolism (IEM) at a reference facility for pediatric care.Cross-sectional, observational and descriptive study with data collection of outpatients, from January 2009 to December 2013. Inclusion criterion: referral to IEM investigation. Exclusion criterion: prior diagnosis of IEM. Analyzed variables: identification data; status of diagnostic investigation; family history of IEM; initial clinical presentation, laboratory abnormalities related to the hypothesis of IEM. Descriptive statistical methods were used in the data analysis.We included 144 patients in the study, of which 62.5% were male. The mean and median ages were, respectively, 4.3 ± 4.7 years and 2.6 years. Twelve patients (8.3%) had a confirmed diagnosis of IEM (three with aminoacidopathies, three with organic acidemias, two with urea cycle disorders and four with lysosomal storage diseases). Cognitive impairment and seizures were the initial signs and symptoms, followed by growth retardation, neuropsychomotor developmental delay, seizures and hepatomegaly. The main laboratory abnormalities in the diagnosis were hyperammonemia and metabolic acidosis.The diagnosis of IEM still creates challenges to the pediatric practice. In this study, we identified the following factors: difficulty to access specific laboratory tests, reduced number of experts and poor dissemination of knowledge among healthcare schools. The early diagnosis of IEM majorly impacts the treatment and prevention of sequelae and should be considered in the initial diagnostic hypotheses.Avaliar a apresentação clínica inicial dos casos com diagnóstico confirmado de erros inatos do metabolismo (EIM) em um serviço de referência em atendimento pediátrico.Estudo clínico, observacional, com delineamento transversal e de coleta retrospectiva em consulta ambulatorial de 2009 a 2013. Critério de inclusão: paciente encaminhado para investigação de EIM. Critério de exclusão: diagnóstico prévio de EIM. Variáveis analisadas: dados de identificação; situação atual da investigação diagnóstica; história familiar; apresentação clínica inicial; alterações laboratoriais. Os dados foram analisados por meio de estatística descritiva.Incluídos 144 pacientes, sendo 62,5% do sexo masculino. A mediana de idade foi de 2,6 anos e a média de 4,3 ± 4,7 anos. Doze pacientes (8,3%) tiveram o diagnóstico confirmado (três com aminoacidopatias, três com acidemias orgânicas, dois com distúrbios do ciclo da ureia e quatro com doenças de depósito lisossômico). Déficit cognitivo e convulsões foram os sinais e sintomas iniciais; seguidos de retardo de crescimento, atraso do desenvolvimento neuropsicomotor, convulsões e hepatomegalia. As principais alterações laboratoriais encontradas foram hiperamonemia e acidose metabólica.O diagnóstico dos EIM ainda traz desafios à prática pediátrica. Neste estudo foram identificados os seguintes fatores: dificuldade de acesso aos exames laboratoriais específicos, reduzido número de especialistas e pouca difusão do conhecimento nas faculdades da área da saúde. O diagnóstico precoce dos EIM tem impacto fundamental no tratamento e prevenção das sequelas, devendo ser considerado já nas hipóteses diagnósticas iniciais.
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- 2017
11. Improvement in time to treatment, but not time to diagnosis, in patients with mucopolysaccharidosis type I.
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Giugliani, Roberto, Muschol, Nicole, Keenan, Hillary A., Dant, Mark, and Muenzer, Joseph
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DIAGNOSIS ,MUCOPOLYSACCHARIDOSIS ,HEMATOPOIETIC stem cell transplantation ,HEMATOPOIETIC stem cells ,DELAYED diagnosis ,DISEASE progression ,RESEARCH ,RESEARCH methodology ,MEDICAL care ,PATIENTS ,ACQUISITION of data ,RETROSPECTIVE studies ,MEDICAL cooperation ,EVALUATION research ,SEVERITY of illness index ,COMPARATIVE studies ,MUCOPOLYSACCHARIDOSIS I ,DRUG therapy - Abstract
Objective: Early diagnosis and treatment initiation are important factors for successful treatment of mucopolysaccharidosis type I (MPS I). The purpose of this observational study was to assess whether age at diagnosis and time to first treatment for individuals with MPS I have improved over the last 15 years.Study Design: Data from the MPS I Registry (NCT00144794) for individuals with attenuated or severe disease who initiated therapy with laronidase enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT) between 1 January 2003 and 31 December 2017 were included.Results: Data were available for 740 individuals with attenuated (n=291) or severe (n=424) MPS I (unknown n=25). Median age at diagnosis for attenuated disease did not change over time and ranged between 4.5 and 6 years of age while the median duration from diagnosis to first ERT decreased from 5.6 years before/during 2004 to 2.4 months in 2014-2017. For severe MPS I treated with HSCT, median age at diagnosis was less than 1 year and median time to first treatment was less than 3 months throughout the 15-year observation period.Conclusions: Times to diagnosis and HSCT initiation for individuals with severe MPS I were consistent over time. For individuals with attenuated MPS I, the time to ERT initiation after diagnosis has improved substantially in the last 15 years, but median age at diagnosis has not improved. Efforts to improve early diagnosis in attenuated MPS I are needed to ensure that patients receive appropriate treatment at the optimal time. [ABSTRACT FROM AUTHOR]- Published
- 2021
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12. Understanding the early presentation of mucopolysaccharidoses disorders : results of a systematic literature review and physician survey
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Clarke, Lorne A., Wijburg, Frits, and Giugliani, Roberto
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Mucopolysaccharidosis III ,Mucopolissacaridoses ,Mucopolysaccharidosis VI ,Diagnóstico ,Mucopolysaccharidosis I ,Diagnosis ,Mucopolysaccharidosis VII ,Mucopolysaccharidosis IV ,Mucopolysaccharidoses ,Mucopolysaccharidosis II - Abstract
As therapies are developed for rare disorders, challenges of early diagnosis become particularly relevant. This article focuses on clinical recognition of mucopolysaccharidoses (MPS), a group of rare genetic diseases related to abnormalities in lysosomal function. As quality of outcomes with current therapies is impacted by timing of intervention, minimizing time to diagnosis is critical. The objective of this study was to characterize how, when, and to whom patients with MPS first present and develop tools to stimulate earlier recognition of MPS. A tripartite approach was used, including a systematic literature review yielding 194 studies, an online physician survey completed by 209 physicians who described 859 MPS cases, and a global panel of MPS experts who distilled the findings. Red flag signs/symptoms were identified for cardiology, pediatric neurology, otorhinolaryngology, rheumatology, orthopedics, pediatrics, and general medicine and converted into simple, specialty-specific tools intended to facilitate early diagnosis of MPS, enabling improved patient outcomes.
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- 2018
13. Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses.
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Corte, Amauri Dalla, de Souza, Carolina F. M., Anés, Maurício, Maeda, Fabio K., Lokossou, Armelle, Vedolin, Leonardo M., Gabriela Longo, Maria, Ferreira, Monica M., Perrone, Solanger G. P., Balédent, Olivier, and Giugliani, Roberto
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MUCOPOLYSACCHARIDOSIS ,CEREBROSPINAL fluid ,MAGNETIC resonance imaging of the brain ,CEREBRAL ventriculography ,CEREBRAL circulation ,DIAGNOSIS - Abstract
Background: Very little is known about the incidence and prevalence of hydrocephalus in patients with mucopolysaccharidoses (MPS). The biggest challenge is to distinguish communicating hydrocephalus from ventricular dilatation secondary to brain atrophy, because both conditions share common clinical and neuroradiological features. The main purpose of this study is to assess the relationship between ventriculomegaly, brain and cerebrospinal fluid (CSF) volumes, aqueductal and cervical CSF flows, and CSF opening pressure in MPS patients, and to provide potential biomarkers for abnormal CSF circulation. Methods: Forty-three MPS patients (12 MPS I, 15 MPS II, 5 MPS III, 9 MPS IV A and 2 MPS VI) performed clinical and developmental tests, and T1, T2, FLAIR and phase-contrast magnetic resonance imaging (MRI) followed by a lumbar puncture with the CSF opening pressure assessment. For the analysis of MRI variables, we measured the brain and CSF volumes, white matter (WM) lesion load, Evans' index, third ventricle width, callosal angle, dilated perivascular spaces (PVS), craniocervical junction stenosis, aqueductal and cervical CSF stroke volumes, and CSF glycosaminoglycans concentration. Results: All the scores used to assess the supratentorial ventricles enlargement and the ventricular CSF volume presented a moderate correlation with the aqueductal CSF stroke volume (ACSV). The CSF opening pressure did not correlate either with the three measures of ventriculomegaly, or the ventricular CSF volume, or with the ACSV. Dilated PVS showed a significant association with the ventriculomegaly, ventricular CSF volume and elevated ACSV. Conclusions: In MPS patients ventriculomegaly is associated with a severe phenotype, increased cognitive decline, WM lesion severity and enlarged PVS. The authors have shown that there are associations between CSF flow measurements and measurements related to CSF volumetrics. There was also an association of volumetric measurements with the degree of dilated PVS. [ABSTRACT FROM AUTHOR]
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- 2017
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14. Minimal clinically important difference for the 6-min walk test: literature review and application to Morquio A syndrome.
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Schrover, Rudolf, Evans, Kathryn, Giugliani, Roberto, Noble, Ian, and Bhattacharya, Kaustuv
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SYNDROMES ,LYSOSOMAL storage diseases ,GENETIC disorders ,DISEASE progression ,RARE diseases ,DRUG therapy ,SYSTEMATIC reviews ,MUCOPOLYSACCHARIDOSIS IV ,DIAGNOSIS - Abstract
Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multi-systemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distribution-based methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy. The literature review showed a mean MCID for the 6MWT of 7% change (range 3-15%) in studies using anchor-based methods and a 9% change (range 4-16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism.
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Giugliani, Roberto, Vairo, Filippo P., Riegel, Mariluce, de Souza, Carolina F. M., Schwartz, Ida V. D., and Pena, Sérgio D. J.
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RARE diseases , *TREATMENT of rare diseases , *METABOLISM , *EQUALITY , *PUBLIC health , *HEALTH insurance , *DIAGNOSIS , *MEDICAL care laws , *INBORN errors of metabolism , *SYMPTOMS - Abstract
Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Clinical course of sly syndrome (mucopolysaccharidosis type VII).
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Montaño, Adriana M., Lock-Hock, Ngu, Steiner, Robert D., Graham, Brett H., Szlago, Marina, Greenstein, Robert, Pineda, Mercedes, Gonzalez-Meneses, Antonio, Çoker, Mahmut, Bartholomew, Dennis, Sands, Mark S., Wang, Raymond, Giugliani, Roberto, Macaya, Alfons, Pastores, Gregory, Ketko, Anastasia K., Ezgü, Fatih, Akemi Tanaka, Arash, Laila, and Beck, Michael
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SLY syndrome ,MUCOPOLYSACCHARIDOSIS ,PATHOLOGICAL physiology ,GLUCURONIDASE ,HYDROPS fetalis ,SKELETAL dysplasia ,DIAGNOSIS - Abstract
Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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17. Management Guidelines for Mucopolysaccharidosis VI.
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Giugliani, Roberto, Harmatz, Paul, and Wraith, James E.
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MUCOPOLYSACCHARIDOSIS treatment , *LYSOSOMAL storage diseases , *THERAPEUTICS , *HEMATOPOIETIC stem cell transplantation , *SYMPTOMS , *CLINICAL trials , *DIAGNOSIS - Abstract
Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease that is characterized by systemic clinical manifestations and significant functional impairment. Diagnosis and management are often challenging because of the considerable variability in symptom presentation and rate of progression. The optimal standard of care should be based on evidence from randomized, controlled trials, meta-analyses, systematic reviews, and expert opinion. In support of this goal, comprehensive management guidelines have been drafted by an international group of experts in the management of patients with mucopolysaccharidosis VI. The guidelines provide a detailed outline of disease manifestations by body system, recommendations for regular assessments, and an overview of current treatment options. [ABSTRACT FROM AUTHOR]
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- 2007
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18. Trends in age of diagnosis and time to treat for MPS I.
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Giugliani, Roberto, Dant, Mark, Keenan, Hillary A., and Muenzer, Joseph
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DIAGNOSIS - Published
- 2020
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19. FAST AND ROBUST PROTOCOL FOR PRENATAL DIAGNOSIS OF MUCOPOLYSACCHARIDOSIS TYPE II.
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Brusius-Facchin, Ana Carolina, Gus, Rejane, Burin, Maira, Sanseverino, Maria Teresa, Magalhães, José Antônio, Giugliani, Roberto, and Leistner-Segal, Sandra
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MEDICAL protocols ,PRENATAL diagnosis ,MUCOPOLYSACCHARIDOSIS II ,SULFATASES ,MEDICAL genetics ,POLYMERASE chain reaction ,AMPLIFICATION reactions ,DIAGNOSIS - Abstract
Introduction: Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal disorder caused by deficiency of iduronate-2-sulfatase (IDS). In this study, we proposed a new protocol for prenatal diagnosis, using DNA obtained from amniotic fluid cells that did not attach to the bottom of the culture flask after the first medium change. Methods: Four pregnant MPS II carriers were referred to the Medical Genetics Service of Hospital de Clinicas de Porto Alegre for a prenatal diagnosis and identification of the disease, which were performed by polymerase chain reaction (PCR) amplification, restriction fragment length polymorphism, and sequencing according to the mutation previously found in the family. Results: The analysis indicated the absence of mutation in three fetal materials and the presence of mutation in one case. Concomitantly, cytogenetic and biochemical analyses were performed after 12 days of cell culture, and only one case showed absence of enzyme activity, confirming the molecular analysis. Conclusions: This diagnostic protocol designed to provide more robust results and safer genetic counseling suggests that DNA obtained from floating amniotic fluid cells can be used as a source of fetal material to allow a faster alternative for prenatal care through molecular analysis. Determination of IDS gene mutation in fetal amniotic fluid cells together with IDS enzyme activity testing is a rapid, sensitive and accurate method for prenatal diagnosis of MPS II for high-risk pregnant women. [ABSTRACT FROM AUTHOR]
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- 2014
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20. Development of a suspicion index tool to aid diagnosis of ASMD disease.
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Wiesinger, Anna-Maria, Lauth, Wanda, Giugliani, Roberto, Muschol, Nicole M., Aries, Charlotte, Moeslinger, Dorothea, Mengel, Eugen, Weghuber, Daniel, and Lagler, Florian
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DIAGNOSIS , *SUSPICION - Published
- 2024
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21. Intrafamilial variability in the clinical presentation of mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS).
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Ficicioglu, Can, Giugliani, Roberto, Harmatz, Paul, Mendelsohn, Nancy, Jego, Virginie, and Parini, Rossella
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MUCOPOLYSACCHARIDOSIS II , *MUCOPOLYSACCHARIDOSIS , *LYSOSOMAL storage diseases , *MEDICAL databases , *HEALTH outcome assessment , *GENETICS , *DIAGNOSIS - Published
- 2017
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22. Expert recommendations for the laboratory diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Diagnostic algorithm and best practice guidelines for a timely diagnosis.
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Giugliani, Roberto, Fietz, Michael, Al-Sayed, Moeenaldeen, Burke, Derek, Cohen-Pfeffer, Jessica, Cooper, Jonathan D., de Halac, Ines Noher, Dvořáková, Lenka, Izzo, Emanuela, Jahnová, Helena, Lukacs, Zoltan, Mole, Sara, Pearce, David, Schulz, Angela, Specchio, Nicola, Xin, Winnie, and Miller, Nicole
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NEURONAL ceroid-lipofuscinosis , *MEDICAL practice , *MEDICAL screening , *MEDICAL research , *HEALTH impact assessment , *DIAGNOSIS - Published
- 2016
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23. Newborn Screening for Pompe Disease.
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Bodamer, Olaf A., Scott, C. Ronald, and Giugliani, Roberto
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FLUORIMETRY , *GLYCOGEN storage disease , *NEWBORN screening , *MASS spectrometry , *MEDICAL protocols , *PEDIATRICS , *MICROFLUIDICS , *MICROFLUIDIC analytical techniques , *SEQUENCE analysis , *PREVENTION , *DIAGNOSIS - Abstract
Started in 1963 by Robert Guthrie, newborn screening (NBS) is considered to be one of the great public health achievements. Its original goal was to screen newborns for conditions that could benefit from presymptomatic treatment, thereby reducing associated morbidity and mortality. With advances in technology, the number of disorders included in NBS programs increased. Pompe disease is a good candidate for NBS. Because decisions regarding which diseases should be included in NBS panels are made regionally and locally, programs and efforts for NBS for Pompe disease have been inconsistent both in the United States and globally. In this article, published in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" guidance supplement, the Pompe Disease Newborn Screening Working Group, an international group of experts in both NBS and Pompe disease, review the methods used for NBS for Pompe disease and summarize results of current and ongoing NBS programs in the United States and other countries. Challenges and potential drawbacks associated with NBS also are discussed. [ABSTRACT FROM AUTHOR]
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- 2017
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24. Molecular and biochemical biomarkers for diagnosis and therapy monitorization of Niemann-Pick type C patients.
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Hammerschmidt, Tatiane Grazieli, de Oliveira Schmitt Ribas, Graziela, Saraiva-Pereira, Maria Luiza, Bonatto, Márcia Polese, Kessler, Rejane Gus, Souza, Fernanda Timm Seabra, Trapp, Franciele, Michelin-Tirelli, Kristiane, Burin, Maira Graeff, Giugliani, Roberto, and Vargas, Carmen Regla
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NIEMANN-Pick diseases , *BIOLOGICAL tags , *MOLECULAR diagnosis , *LYSOSOMAL storage diseases , *MENTAL illness , *DIAGNOSIS , *THERAPEUTICS - Abstract
Background Niemann-Pick type C (NP-C), one of 50 inherited lysosomal storage disorders, is caused by NPC protein impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. The clinical manifestations of NP-C include hepatosplenomegaly, neurological and psychiatric symptoms. Current diagnosis for NP-C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining. Lately, two metabolites that are markedly increased in NP-C patients are arising as biomarkers for this disease screening: 7-ketocholesterol and cholestane-3β,5α,6β-triol, both oxidized cholesterol products. Objective In this work, we aimed to evaluate the performance of cholestane-3β,5α,6β-triol analysis for the screening and monitoring of NPC patients, correlating it with chitotriosidase levels, Filipin staining and molecular analysis. It was investigated 76 non-treated individuals with NP-C suspicion and also 7 patients with previous NP-C diagnosis under treatment with miglustat, in order to verify the cholestane-3β,5α,6β-triol value as a tool for therapy monitoring. Results Considering molecular assay as golden standard, it was verified that cholestane-3β,5α,6β-triol analysis presented 88% of sensitivity, 96.08% of specificity, a positive and negative predictive value calculated in 91.67% and 94.23%, respectively, for the diagnosis of NP-C. Chitotriosidase levels were increased in patients with positive molecular analysis for NP-C. For Filipin staining, it was found 1 false positive, 7 false negative and 24 inconclusive cases, showing that this assay has important limitations for NP-C diagnosis. Besides, we found a significant decrease in cholestane-3β,5α,6β-triol concentrations in NP-C patients under therapy with miglustat when compared to non-treated patients. Conclusion Taken together, the present data show that cholestane-3β,5α,6β-triol analysis has a high potential to be an important NP-C screening assay, and also can be used for therapy monitorization with miglustat in NP-C patients. [ABSTRACT FROM AUTHOR]
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- 2018
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25. Treatment of brain disease in the mucopolysaccharidoses.
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Scarpa, Maurizio, Orchard, Paul J., Schulz, Angela, Dickson, Patricia I., Haskins, Mark E., Escolar, Maria L., and Giugliani, Roberto
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MUCOPOLYSACCHARIDOSIS , *MUCOPOLYSACCHARIDOSIS treatment , *LYSOSOMAL storage diseases , *GLYCOSAMINOGLYCANS , *BRAIN disease treatment , *DIAGNOSIS - Abstract
The mucopolysaccharidosis (MPS) disorders are a group of lysosomal storage diseases caused by lysosomal enzyme deficits that lead to glycosaminoglycan accumulation, affecting various tissues throughout the body based on the specific enzyme deficiency. These disorders are characterized by their progressive nature and a variety of somatic manifestations and neurological symptoms. There are established treatments for some MPS disorders, but these mostly alleviate somatic and non-neurological symptoms and do not cure the disease. Patients with MPS I, II, III, and VII can present with neurological manifestations such as neurocognitive decline and behavioral problems. Treatment of these neurological manifestations remains challenging due to the blood-brain barrier (BBB) that limits delivery of therapeutic agents to the central nervous system (CNS). New therapies that circumvent this barrier and target brain disease in MPS are currently under development. They primarily focus on facilitating penetration of drugs through the BBB, delivery of recombinant enzyme to the brain by gene therapy, or direct CNS administration. This review summarizes existing and potential future treatment approaches that target brain disease in MPS. The information in this review is based on current literature and presentations and discussions during a closed meeting by an international group of experts with extensive experience in managing and treating MPS. [ABSTRACT FROM AUTHOR]
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- 2017
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26. Consensus recommendation on a diagnostic guideline for acid sphingomyelinase deficiency.
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Wasserstein, Melissa, Dionisi-Vici, Carlo, Giugliani, Roberto, Hwu, Paul, Lidove, Olivier, Lukacs, Zoltan, Mengel, Eugen, Mistry, Pramod, Schuchman, Edward, and McGovern, Margaret
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NIEMANN-Pick diseases , *RETICULOENDOTHELIAL diseases , *DISEASE progression , *TREATMENT effectiveness , *DIAGNOSIS , *THERAPEUTICS - Published
- 2017
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27. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure.
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Van Der Lee, Johanna H., Morton, Jonathan, Adams, Heather R., Clarke, Lorne, Ebbink, Berendine Johanne, Escolar, Maria L., Giugliani, Roberto, Harmatz, Paul, Hogan, Melissa, Jones, Simon, Kearney, Shauna, Muenzer, Joseph, Rust, Stewart, Semrud-Clikeman, Margaret, Wijburg, Frits A., Yu, Zi-Fan, Janzen, Darren, and Shapiro, Elsa
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ADAPTABILITY (Personality) in children , *LYSOSOMAL storage diseases , *CENTRAL nervous system , *COGNITIVE ability , *CLINICAL trials , *DIAGNOSIS - Abstract
The design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here. [ABSTRACT FROM AUTHOR]
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- 2017
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28. Prenatal diagnosis of Pompe disease.
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Netto, Alice Brinckmann Oliveira, Brusius-Facchin, Ana Carolina, Leistner-Segal, Sandra, Kessler, Rejane Gus, Tirelli, Kristiane M., Pasetto, Fernanda B., Sebastião, Fernanda M., Kubaski, Francyne, de Camargo Pinto, Louise Lapagesse, and Giugliani, Roberto
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GLYCOGEN storage disease type II , *PRENATAL diagnosis , *DIAGNOSIS - Published
- 2023
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29. Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.
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Biancini, Giovana Brondani, Jacques, Carlos Eduardo, Hammerschmidt, Tatiane, de Souza, Heryk Motta, Donida, Bruna, Deon, Marion, Vairo, Filippo Pinto, Lourenço, Charles Marques, Giugliani, Roberto, and Vargas, Carmen Regla
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ANGIOKERATOMA corporis diffusum , *LYSOSOMAL storage diseases , *THERAPEUTICS , *GALACTOSIDASES , *PATHOLOGICAL physiology , *BIOMOLECULES , *LIPID peroxidation (Biology) , *DIAGNOSIS - Abstract
Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase – GPx – and normal glutathione reductase – GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO . ) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO . equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD. [ABSTRACT FROM AUTHOR]
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- 2016
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30. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis.
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Fietz, Michael, AlSayed, Moeenaldeen, Burke, Derek, Cohen-Pfeffer, Jessica, Cooper, Jonathan D., Dvořáková, Lenka, Giugliani, Roberto, Izzo, Emanuela, Jahnová, Helena, Lukacs, Zoltan, Mole, Sara E., Noher de Halac, Ines, Pearce, David A., Poupetova, Helena, Schulz, Angela, Specchio, Nicola, Xin, Winnie, and Miller, Nicole
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NEURONAL ceroid-lipofuscinosis , *LYSOSOMAL storage diseases , *NEURODEGENERATION , *GENETIC mutation , *HISTORY of medicine , *DIAGNOSIS - Abstract
Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 ( TPP1 )/ CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2–4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1 / CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease. [ABSTRACT FROM AUTHOR]
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- 2016
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31. Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy.
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Uribe-Cruz, Carolina, Kieling, Carlos Oscar, López, Mónica Luján, Osvaldt, Alessandro, Ochs de Muñoz, Gustavo, Silveira, Themis Reverbel da, Giugliani, Roberto, and Matte, Ursula
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BONE marrow cells , *HEPATECTOMY , *LIVER failure , *GENE expression , *GLUCURONIDASE genetics , *DIAGNOSIS , *TRANSPLANTATION of organs, tissues, etc. , *PHYSIOLOGY - Abstract
Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival. [ABSTRACT FROM AUTHOR]
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- 2015
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32. Shotgun proteomics reveals possible mechanisms for cognitive impairment in Mucopolysaccharidosis I mice.
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Baldo, Guilherme, Lorenzini, Daniel Macedo, Santos, Diogenes Santiago, Mayer, Fabiana Quoos, Vitry, Sandrine, Bigou, Stephanie, Heard, Jean Michael, Matte, Ursula, and Giugliani, Roberto
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PROTEOMICS , *MILD cognitive impairment , *MUCOPOLYSACCHARIDOSIS I , *LABORATORY mice , *IDURONIDASE , *INTELLECTUAL disabilities , *DIAGNOSIS - Abstract
Mucopolysaccharidosis type I (MPS I) is due to deficient alpha-L-iduronidase (IDUA) which leads to storage of undegraded glycosaminoglycans (GAG). The severe form of the disease is characterized by mental retardation of unknown etiology. Trying to unveil the mechanisms that lead to cognitive impairment in MPS I, we studied alterations in the proteome from MPS I mouse hippocampus. Eight-month old mice presented increased LAMP-1 expression, GAG storage in neurons and glial cells, and impaired aversive and non-aversive memory. Shotgun proteomics was performed and 297 proteins were identified. Of those, 32 were differentially expressed. We found elevation in proteins such as cathepsins B and D; however their increase did not lead to cell death in MPS I brains. Glial fibrillary acid protein (GFAP) was markedly elevated, and immunohistochemistry confirmed a neuroinflammatory process that could be responsible for neuronal dysfunction. We didn't observe any differences in ubiquitin expression, as well as in other proteins related to protein folding, suggesting that the ubiquitin system is working properly. Finally, we observed alterations in several proteins involved in synaptic plasticity, including overexpression of post synaptic density-95 (PSD95) and reduction of microtubule-associated proteins 1A and 1B. These results together suggest that the cognitive impairment in MPS I mice is not due to massive cell death, but rather to neuronal dysfunction caused by multiple processes, including neuroinflammation and alterations in synaptic plasticity. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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33. Avaliação de processos de coleta e transporte de amostras biológicas para diagnósticos de erros inatos do metabolismo em centros de referência
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Trapp, Franciele Barbosa, Giugliani, Roberto, and Facchin, Ana Carolina Brusius
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Genética médica ,Biological samples ,Serviços de laboratório clínico ,Collect ,Bancos de espécimes biológicos ,Erros inatos do metabolismo ,Diagnóstico ,Manejo de espécimes ,Diagnosis ,Transport ,Inborn errors of metabolism - Abstract
Introdução: A coleta e o transporte de amostras biológicas fazem parte da fase pré- analítica do processo operacional de realização de exames laboratoriais, sendo essa uma fase crítica para as análises. O Serviço de genética Medica (SGM) do Hospital de Clínicas de Porto Alegre (HCPA) é conhecido como um centro de referência nacional e internacional em diagnóstico laboratorial e pesquisa de diferentes doenças genéticas raras, onde são recebidas amostras de todo Brasil e diversos outros países. Devido à importância das avaliações laboratoriais e com o avanço tecnológico na área de diagnósticos verificamos a necessidade de investigação e otimização dos processos de coleta e transporte de amostras biológicas. Objetivo: O principal objetivo desse projeto foi avaliar diferentes métodos de coleta e transporte de amostras biológicas para a realização de testes diagnósticos para erros inatos do metabolismo, assim facilitando o acesso ao diagnóstico, minimizando o número de solicitações de novas amostras, bem como apoiar o desenvolvimento de pesquisas na área. Metodologia: O presente trabalho avaliou 2848 amostras biológicas encaminhadas para o Serviço de Genética Médica do HCPA por 276 instituições, de 25 estados diferentes, verificamos os dados de identificação, volume, temperatura de transporte, tempo decorrido entre a coleta e o transporte em comparação com diferentes sistemas de coleta utilizados pelos serviços associados às redes, entre si e com um sistema padrão desenvolvido pelo nosso serviço. Após uma avaliação inicial realizamos também uma intervenção com material informativo, estratégias educacionais, treinamento de profissionais sobre procedimentos adequados de coleta, remessa e transporte de amostras biológicas. Resultados: 1308 amostras foram enviadas pré-intervenção sendo que destas 254 (19%) apresentaram alguma inconformidade. Após a realização da intervenção através do uso de instruções de coleta e envio uma redução de 62% foi encontrada (119 amostras de 1540). Conclusão: Uma redução considerável no número de amostras inadequadas para uso foi obtida através do uso deste material informativo, tal redução tem considerável impacto nos exames de pesquisa e assistência do HCPA. Este projeto contribuiu para o aperfeiçoamento dos processos de coleta, armazenamento e transporte de material biológico. Protocolos como este podem vir a proporcionar a melhora na qualidade do serviço diagnóstico prestado no SGM e demais utilizadores deste. Além disto, o diagnóstico precoce de uma doença genética poderá facilitar a intervenção mais precoce, através de tratamentos que sabidamente tem um melhor resultado quanto mais cedo se iniciar. Além do mais, o impacto de um diagnóstico preciso e precoce é extremamente benéfico para o sistema de saúde, visando também fortalecer e dar continuidade ao treinamento dos profissionais de saúde e divulgação de informações especializadas. Introduction: The collection and the transport of biological samples belong to the preanalytical phase of laboratory tests, which is a critical step for the analyzes. The Medical Genetics Service (SGM) of Hospital de Clínicas de Porto Alegre (HCPA) is a national and an international reference center for the diagnosis and research of rare genetic diseases, receiving samples from Brazil and several other countries. Due to the importance of laboratory evaluations and technological advances in the area, we verified the need for investigation and optimization of biological sample collection and the transport processes. Objective: The main objective of this project was to evaluate different methods for collecting and transporting biological samples to perform diagnostic tests for inborn errors of metabolism, facilitating access to diagnosis, minimizing the number of requests for new samples, as well as supporting research in the area. Methodology: This study has evaluated 2,848 samples from 276 centers from 25 Brazilian states. We have verified the sample information, the sample volume, temperature of transport, time between sample collection and shipping and we have compared the different collection systems offered by the several networks with a standardized system created by our service. After an initial evaluation prior to any intervention we have also evaluated the efficacy of this novel protocol in order to reduce the need of sample recollection by the use of an informative sheet that lead to the training of health professionals with information regarding sample collection, shipping and transportation of biological samples. Results: 1308 samples were evaluated before the educational intervention, 254 (19%) out of these had at least one nonconformity. After the use of the educational sheet that had information about sample collection and shipping there was a reduction of 11.3% in the preanalytical erros (119 samples out of 1,540). Conclusions: A substantional reduction in the number of inappropriate samples was obtained after the use of this informative material. This reduction has great impact in our health care at the HCPA. This project has contributed to aid sample collection, storage and shipping. Such educational protocols can help to improve the quality of our diagnostic procedures as well as of other services. Besides, early diagnosis of genetic disorders can aid early intervention that is well known to have greater outcomes. Furthermore, the impact of a precise early diagnosis is beneficial to our health system aiming to strengthen the training of health professionals as to spread revelant information.
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- 2019
34. Diagnóstico de mucopolissacaridose tipo IVA em amostras de sangue impregnado em papel filtro
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Camelier, Marli Teresinha Viapiana and Giugliani, Roberto
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Sulfato de ceratano ,Mucopolissacaridose IV ,Mucopolissacaridoses ,Diagnosis ,Dried blood samples ,Morquio syndrome ,Keratan sulfate ,Glicosaminoglicanas ,Mucopolysaccharidosis ,Glycosaminoglycans - Abstract
INTRODUÇÃO: As mucopolissacaridoses (MPS) são doenças de depósito lisossômico, caracterizadas pela deficiência de enzimas lisossômicas envolvidas na degradação dos glicosaminoglicanos (GAGs). O acúmulo anormal dessas macromoléculas no interior dos lisossomos provoca alterações estruturais e funcionais, de caráter multissistêmico e progressivo. Os GAGs acumulados também são excretados na urina, onde podem ser identificados através de diversos métodos bioquímicos. Estas doenças estão presentes em todos os grupos étnicos e a incidência conjunta das MPS, é estimada entre 1:10.000 a 1:25.000 nascidos vivos. (Baehner, 2005). A causa das MPS é a deficiência de uma enzima específica na rota de degradação dos GAGs. As MPS são classificadas segundo o tipo de substrato (GAGs) acumulado e a enzima específica deficiente. Na síndrome de Morquio A, ou mucopolissacaridose tipo IVA (MPS IVA), o substrato acumulado é o queratan sulfato e a enzima deficiente é a N-acetilgalactosamina-6-sulfatase. (GALNS). Os pacientes afetados por MPS IVA apresentam baixa estatura, disostose múltipla, opacidade de córnea, entre outros sinais e sintomas. O desenvolvimento psicomotor e mental é normal. O método de detecção inicial das MPS baseia-se na identificação dos GAGs, que são excretados em excesso na urina destes pacientes. A presença de queratan sulfato na eletroforese ou a detecção de níveis aumentados na dosagem quantitativa, direciona a investigação laboratorial para a MPS IV. O diagnóstico definitivo se estabelece através da medida da atividade enzimática em leucócitos ou fibroblastos, onde se constata a deficiência enzimática. OBJETIVOS: Este estudo teve como objetivo principal, tornar disponível um novo método, mais simples, rápido e acessível, para o diagnóstico bioquímico de mucopolissacaridose tipo IVA, utilizando amostras de sangue impregnadas em papel filtro (SIPF). MATERIAIS E MÉTODOS: Amostras de SIPF e leucócitos de 35 pacientes de ambos os sexos, com idade entre 3 e 47 anos, com diagnóstico previamente estabelecido de MPS IVA, pelo método convencional, em leucócitos e /ou fibroblastos, foram analisadas. Para o estabelecimento dos valores de referência, foram estudadas amostras de leucócitos e de SIPF de 54 indivíduos saudáveis (18-50 anos), de ambos os sexos. Após assinatura do termo de consentimento, amostras de sangue periférico de pacientes e controles, foram coletadas, para a obtenção de leucócitos e sangue impregnado em papel filtro.(SIPF). Os ensaios enzimáticos foram realizados nas amostras de leucócitos e SIPF, simultaneamente, para comparar os resultados. RESULTADOS: Os resultados obtidos nos ensaios enzimáticos de todos os pacientes apresentando MPS IVA, confirmaram a deficiência da atividade enzimática em ambos materiais (leucócitos e SIPF) com uma diferença estatisticamente significativa em relação ao grupo controle. (Mann-Witney U test, p< 0,001). Neste estudo, a medida de GALNS em amostras de SIPF permitiu a identificação dos pacientes com MPS IVA, com sensibilidade de 100 %. Os testes de estabilidade realizados nas amostras de SIPF indicaram que amostras coletadas para a medida da atividade de GALNS devem ser mantidas a 4ºC sempre que possível, sendo estáveis nesta temperatura por mais de 30 dias. CONCLUSÕES: Nas condições utilizadas, amostras de SIPF se mostraram adequadas para a identificação segura de pacientes com MPS tipo IVA. O método que utiliza amostras de SIPF é mais acessível e rápido, simplificando a etapa de coleta e transporte, podendo ser utilizado para detectar pacientes afetados, especialmente em áreas de difícil acesso para a coleta e transporte de amostras líquidas. INTRODUCTION: Mucopolysaccharidosis (MPS) are lysosomal deposit diseases characterized by lysosomal enzymes deficiency involved in the degradation of glycosaminoglycans (GAGs). The abnormal accumulation of these macromolecules inside the lysosomes provokes structural and functional alterations multi-systemically and progressively. The accumulated GAGs are also excreted in the urine, where they may be identified through many different biochemical methods. These diseases occur among all ethnical groups and the combined incidence of MPS is estimated at 1:10.000 to 1:25.000 live births. (Baehner, 2005). The MPS’ cause is the deficiency of a specific enzyme in the GAGs degradation route. The MPS are classified according to a type of substrate accumulated (GAGs) and the deficiency of a specific enzyme. In Morquio syndrome A or Mucopolysaccharidosis type IVA (MPS IVA), the accumulated substrate is the keratan sulfate and the deficient enzyme is the N-acetylgalactosamine-6-sulfatase (GALNS). The patients affected by MPS IVA present short stature, dysostosis multiplex, corneal opacity, among others signs and symptoms. The cognitive and mental developments are normal. The MPS initial detection method is based on the identification of the GAGs which are excreted in the patients’ urine. The presence of the keratan sulphate in the electrophoresis or the detection of the increased levels in the quantitative dosage directs the laboratory investigation to MPS IV. The definitive diagnosis is established through measuring the enzymatic activity in leukocytes or fibroblasts, in which the enzymatic deficiency is proved. OBJECTIVE: This study’s main purpose is to offer an original, simpler, faster and more accessible method for biochemical diagnosis of Mucopolysaccharidosis type IVA using dried blood samples (DBS). MATERIALS AND METHODS: DBS and leukocytes from 35 patients from both sexes between 3 and 47 years of age with previously established diagnosis of MPS IVA through the conventional method in leukocytes and/or fibroblasts were analyzed. In order to establish reference values DBS and leukocytes samples from 54 healthy people (18-50 years of age) from both sexes were studied. After signing a paper consent form, peripheral blood samples from patients and controls were collected for obtaining leukocytes and dried blood samples (DBS). To validate the method, we made a simultaneous GALNS assay in leukocytes and DBS. RESULTS: The results obtained in the enzymatic assays from all patients presenting MPS IVA confirmed the deficiency of enzymatic activity in both materials (leukocytes and DBS) with a significant statistical difference in relation to the control group. (Mann-Witney U tes, p< 0,001). In this study, the quantity of GALNS in DBS allowed the identification of patients with MPS IVA with sensibility of 100%. The stability tests indicate that DBS samples collected for measuring the activity of GALNS must be kept at 4ºC whenever possible, being stable in this temperature for more than 30 days. CONCLUSION: In the used conditions, DBS were adequate for a safe identification of patients with MPS type IVA. The method which utilizes DBS is cheaper and faster, what simplifies the collection and transportation stage and can be used to detect affected patients especially in difficult access areas for the collection and transportation of liquid samples.
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- 2011
35. An algorithm to assess the need for CSF shunting in mucopolysaccharidosis patients.
- Author
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Dalla-Corte, Amauri, Souza, Carolina F.M., Vairo, Filippo, Vedolin, Leonardo M., Longo, Maria G., Anés, Maurício, Maeda, Fábio K., Federhen, Andressa, Rosa, Amanda T., and Giugliani, Roberto
- Subjects
- *
MUCOPOLYSACCHARIDOSIS , *CEREBROSPINAL fluid examination , *MAGNETIC resonance imaging of the brain , *HEART beat , *RADIOLOGY , *DIAGNOSIS - Published
- 2017
- Full Text
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36. Characteristics of patients with mucopolysaccharidosis type II (MPS II) diagnosed aged < 5 years: data from the Hunter Outcome Survey (HOS).
- Author
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Harmatz, Paul, Lin, Shuan-Pei, Muenzer, Joseph, Giugliani, Roberto, Guffon, Nathalie, Jego, Virginie, and Burton, Barbara K.
- Subjects
- *
MUCOPOLYSACCHARIDOSIS II , *MILD cognitive impairment , *HISTORY of medicine , *HEALTH surveys , *CLINICAL trials , *DIAGNOSIS - Published
- 2017
- Full Text
- View/download PDF
37. Investigation of newborns screened in a pilot program for four lysosomal diseases in Brazil.
- Author
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Bravo-Villalta, Heydy V, Neto, Eurico C, Schulte, Jaqueline, Pereira, Jamile, Sampaio-Filho, Cláudio, Burin, Maira G, Bitencourt, Fernanda H, Sebastião, Fernanda M, Guidobono, Régis R, Brusius-Facchin, Ana C, Pasqualim, Gabriela, Rojas-Málaga, Diana E, Matte, Ursula S, and Giugliani, Roberto
- Subjects
- *
LYSOSOMAL storage diseases , *MEDICAL screening , *PILOT projects , *MEDICAL research , *DIAGNOSIS ,DIAGNOSIS of neonatal diseases - Published
- 2017
- Full Text
- View/download PDF
38. Sanfilippo syndrome type B: a review of patients diagnosed by the MPS Brazil Network.
- Author
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Federhen, Andressa, Poswar, Fabiano Oliveira, Trapp, Franciele Barbosa, da Rosa, Heluísa Castagnino, Silva, Laysla Pedelhes, Rocha, Daniele Lima, Burin, Maira Graeff, Guidobono, Regis R, De Mari, Jurema F, Bitencourt, Fernanda, Leistner-Segal, Sandra, Facchin, Ana Carolina Brusius, Matte, Ursula Silveira, and Giugliani, Roberto
- Subjects
- *
SANFILIPPO syndrome , *MUCOPOLYSACCHARIDOSIS , *MEDICAL genetics , *DIAGNOSIS , *PATIENTS - Published
- 2017
- Full Text
- View/download PDF
39. Placenta analysis of prenatally diagnosed patients reveals early GAG storage in mucopolysaccharidoses II and VI
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Baldo, Guilherme, Matte, Ursula, Artigalas, Osvaldo, Schwartz, Ida Vanessa, Burin, Maira Graeff, Ribeiro, Erlane, Horovitz, Dafne, Magalhaes, Tatiana Pacheco, Elleder, Milan, and Giugliani, Roberto
- Subjects
- *
MUCOPOLYSACCHARIDOSIS , *PRENATAL diagnosis , *GLYCOSAMINOGLYCANS , *PLACENTA , *LYSOSOMAL storage diseases , *PREGNANCY complications , *ELECTRON microscopy , *DIAGNOSIS of fetal diseases , *DIAGNOSIS - Abstract
Abstract: We analyzed placental tissue in one fetus with MPS II (iduronate sulphatase deficiency) and another with MPS VI (arylsulfatase B deficiency). Both were diagnosed prenatally, but families decided to continue pregnancies and placentas were collected at birth. We were able to demonstrate early storage of GAGs in both diseases by GAG measurement and microscopy analysis. Our results suggest that some alterations related to MPS storage, although not pronounced, may be observed in placental tissue of patients affected by MPS II and MPS VI. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
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40. Novel heparan sulfate assay by using automated high throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses.
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Tomatsu, Shunji, Shimada, Tsutomu, LaMarr, William A., Vlies, Naomi V., Yasuda, Eriko, Mason, Robert W., Kubaski, Francyne, Giugliani, Roberto, Yamaguchi, Seiji, Suzuki, Yasuyuki, and Orii, Tadao
- Subjects
- *
HEPARAN sulfate , *MUCOPOLYSACCHARIDOSIS , *GLYCOSAMINOGLYCANS , *LIQUID chromatography-mass spectrometry , *SOLID phase extraction , *DIAGNOSIS - Published
- 2015
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- View/download PDF
41. MPS I and MPS II: Minimal estimated incidence in Brazil and comparison to the rest of the world.
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Federhen, Andressa, de Cássia Cascaes Batista, Carla, Burin, Maira, Leistner-Segal, Sandra, Matte, Ursula, Rafaelli, Célio, Bender, Fernanda, Brusius, Ana Carolina, Pasqualim, Gabriela, and Giugliani, Roberto
- Subjects
- *
LYSOSOMAL storage diseases , *THERAPEUTICS , *DISEASE incidence , *EPIDEMIOLOGY , *COMPARATIVE studies , *DIAGNOSIS - Published
- 2015
- Full Text
- View/download PDF
42. Diagnosing communicating hydrocephalus in mucopolysaccharidoses: Correlation between cerebrospinal fluid flow imaging and lumbar pressure studies.
- Author
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de Souza, Carolina Fischinger Moura, Corte, Amauri Dalla, Vairo, Filippo, Anés, Mauricio, Vedolin, Leonardo Modesti, Ferreira, Monica Moraes, Aguzzoli, Adriano de Alencastro Guimaraes, Perrone, Solanger Graciana Paulão, Federhen, Andressa, and Giugliani, Roberto
- Subjects
- *
HYDROCEPHALUS , *MUCOPOLYSACCHARIDOSIS , *CEREBROSPINAL fluid , *BRAIN imaging , *STATISTICAL correlation , *MEDICAL statistics , *DIAGNOSIS - Published
- 2015
- Full Text
- View/download PDF
43. Galactocerebrosidase assay on dried-leukocytes impregnated in filter paper for the detection of Krabbe disease.
- Author
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Camelier, Marli, Civallero, Gabriel, De Mari, Jurema, Burin, Maira, and Giugliani, Roberto
- Subjects
- *
GLOBOID cell leukodystrophy , *ENZYME-linked immunosorbent assay , *LEUCOCYTES , *CLINICAL trials , *DIAGNOSIS , *THERAPEUTICS - Published
- 2015
- Full Text
- View/download PDF
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