Search

Background: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres., Methods: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups., Results: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects., Conclusion: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To evaluate lower urinary tract symptoms (LUTS) in children with infantile-onset Pompe disease (IOPD) who received early treatment., Methods: Pompe disease (PD), or glycogen storage disease II is a rare autosomal recessive lysosomal storage disease that affects multiple organ systems. To our knowledge, only one study has focused on the relationship between LUTS and incontinence in children with PD. This cross-sectional study was conducted from August 2019 through March 2021 and children with IOPD, who had received early and regular enzyme replacement therapy, were enrolled. Participants or their parents completed the Dysfunctional Voiding Scoring System (DVSS) questionnaire. All children underwent uroflowmetry and postvoid residual urine measurements. Fourteen children (age, 4-9 years) with IOPD were enrolled., Results: Ten patients (71.4%) had abnormal uroflow curves. In addition, results of the DVSS revealed that approximately half (42.9%) of our IOPD patients had voiding dysfunction, with urinary incontinence as the most common symptom (64.3%, 9/14). No significant correlations were found between LUTS and uroflow curves in children with IOPD., Conclusions: The frequency of LUTS and lower urinary tract dysfunction noted on uroflowmetry should encourage pediatricians to actively identify IOPD patients with LUTS, regardless of the timing and frequency of their treatments, and refer them to a urologist for further evaluation and appropriate treatment., (© 2022 Wiley Periodicals LLC.)

This study evaluates the whole airway abnormalities of long-term treated late-onset Pompe disease (LOPD) patients, with interventions using the flexible bronchoscope (FB). As a retrospective study, we follow up with our five LOPD patients treated with Myozyme from 2012 to 2021 regularly, but with a focus on the whole airway abnormalities of these patients visualized through FB. The long-term clinical outcomes and relevant airway symptoms were assessed. Pulmonary function test and polysomnography were performed to evaluate the degree of respiratory compromise. All patients in the study had varying degrees of airway collapsibility, pulmonary complications, sleep apnea syndrome, and facial anomalies. Pulmonary function could preserve after Myozyme treatment, but potential deterioration thereafter. This is the first study that focuses on airway abnormalities and pulmonary complications in long-term treated LOPD patients using FB. Despite years of Myozyme treatment, we still observed airway abnormalities in these patients. In our series, the pulmonary complications seem more obvious than those observed in patients with infantile-onset Pompe disease, which might be related to the late diagnosis and treatment. We might recommend that FB could provide dynamic evaluation and interventions of airway abnormalities simultaneously. Early diagnosis of respiratory dysfunction is a critical prognostic factor of the long-term outcome of treated LOPD patients., (© 2021 Wiley Periodicals LLC.)

Background: Studies suggest that enzyme-replacement therapy (ERT) is crucial to the survival of patients with infantile-onset Pompe disease (IOPD). Hearing impairment (HI) is one of the clinical sequelae observed in long-term survivors. However, the benefits of early ERT for hearing outcomes have not yet been reported. This study aimed to investigate the impact of early ERT on IOPD patients., Methods: This retrospective longitudinal study recruited IOPD patients who were referred by newborn screening for confirmatory diagnosis based on our rapid diagnostic criteria and received early ERT treatment between January 1, 2010, and January 31, 2018. The hearing test battery included a tympanogram, otoacoustic emission, auditory brainstem evoked response (ABR), pure-tone audiometry or conditioned play audiometry., Results: Nineteen patients with IOPD were identified, 6 of whom had hearing impairment (HI); 1 had conductive HI, 2 had sensorineural HI (one had bilateral mild HI and one had mild HI in a single ear) and 1 had moderate mixed-type HI. Two patients failed the newborn screening test and had mild HI in the ABR. The mean age of the initial time to ERT was 11.05 ± 4.31 days, and the HI rate was 31.6% (6/19)., Conclusion: Our study is the largest cohort to show the characteristic hearing outcomes of IOPD patients after ERT. Early ERT within 2 weeks after birth may contribute to better hearing outcomes. Clinicians should be vigilant in testing for the hearing issues associated with IOPD and should intervene early if any HI is detected., (© 2021. The Author(s).)

Early enzyme replacement therapy (ERT) improve long-term outcomes in patients with infantile-onset Pompe disease (IOPD). Our cohort of patients with IOPD at Taipei Veterans General Hospital (TVGH) joined Taiwan Pompe newborn screening program from 2008, testing more than one million newborns until 2018. By 2010, we had established rapid diagnostic strategies. Now, the average age of ERT initiation starts at an average age of <10 days-old, the earliest group in the world. However, they still presented some airway problems. We present a retrospective study focused on airway abnormalities in these patients along 8 years of observation. Fifteen patients with IOPD, who received very early treatment at a mean age of 8.94 ± 3.75 days, underwent flexible bronchoscopy (FB) for dynamic assessment of the whole airway. Long-term clinical outcomes and relevant symptoms of the upper airway were assessed. All patients in the study had varying degrees of severity of upper airway abnormalities and speech disorders. The three oldest children (Age 94, 93, and 88 months, respectively) had poor movement of the vocal cords with reduced abduction and adduction and had silent aspiration of saliva through the glottis during respiration. This is the largest cohort study presented to date about airway abnormalities in very early treated patients with IOPD patients by FB. Despite very early treatment, we observed upper airway abnormalities in these IOPD patients. In IOPD, upper airway abnormalities seem inevitable over time. We suggest early and continuous monitoring for all IOPD patients, even with early and regular treatment., (© 2020 Wiley Periodicals, Inc.)

Our study aimed to evaluate the utility of muscle ultrasound in newborn screening of infantile-onset Pompe disease (IOPD) and to establish a system of severity grading. We retrospectively selected 35 patients with initial low acid alpha-glucosidase (GAA) activity and collected data including muscle ultrasound features, GAA gene mutation, activity/performance, and pathological and laboratory findings. The echogenicity of 6 muscles (the bilateral vastus intermedius, rectus femoris, and sartorius muscles) was compared to that of epimysium on ultrasound and rated either 1 (normal), 2 (mildly increased), or 3 (obviously increased). These grades were used to divide patients into 3 groups. IOPD was present in none of the grade-1 patients, 5 of 9 grade-2 patients, and 5 of 5 grade-3 patients (P < .001). Comparing grade-2 plus grade-3 patients to grade-1 patients, muscle ultrasound detected IOPD with a sensitivity and specificity of 100.0% (95% confidence interval [CI]: 69.2%-100%) and 84.0% (95% CI: 63.9%-95.5%), respectively. The mean number of affected muscles was larger in grade-3 patients than in grade-2 patients (4.2 vs. 2.0, P = .005). Mean alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) levels were differed significantly different between grade-3 and grade-1 patients (P < .001). Because it permits direct visualization of injured muscles, muscle ultrasound can be used to screen for IOPD. Our echogenicity grades of muscle injury also correlate well with serum levels of muscle-injury biochemical markers.

Background: Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up., Methods: We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied., Results: With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group., Conclusions: The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease., (© 2017 American Association for Clinical Chemistry.)

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age., (© The Author(s) 2016.)

Objective: To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies., Methods: In this nationwide program, 669,797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital., Results: After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid α-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 ± 1.3 months, the same age as normal children., Conclusions: ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes., (Copyright © 2016. Published by Elsevier Inc.)

Pompe disease is a rare autosomal recessive disorder caused by α-glucosidase deficiency. Lower airway involvement and management are rare in patients with late-onset Pompe disease. We describe the case of a 16-y-old girl with late-onset Pompe disease who presented with obvious progressive deterioration in respiratory function. Pulmonary hypertension was also apparent on echocardiography. She had been on enzyme replacement therapy and nighttime CPAP ventilation for several years. Flexible bronchoscopy was used for diagnosis and subsequent implantation of a bronchial airway stent. Following implantation of the stent, the patient's pulmonary function stabilized, and her pulmonary hypertension resolved. The patient continued on enzyme replacement therapy and nighttime CPAP ventilation. This case highlights that lower airway involvement may occur with late-onset Pompe disease and that flexible bronchoscopy can be an effective tool for both diagnosis and management of lower airway collapse in late-onset Pompe disease., (Copyright © 2015 by Daedalus Enterprises.)

The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m(2)). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes., (© 2013 Wiley Periodicals, Inc.)

The article presents a study on the diagnosis of the cardiac variant of the Fabry disease through newborn screening. Disease incidence were ascertained in the Taiwan Chinese population using the newborn screening program based on the assessment of the enzyme activity. Results show that Fabry mutations among newborns were high, highlighting the importance of early detection to allow therapeutic intervention with enzyme replacement therapy.

Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms. [ABSTRACT FROM AUTHOR]