Search

Fatty acid oxidation disorders (FAODS) consist of rare diseases which affect the energy production of the mitochrondria by disrupting the β-oxidation of fatty acid, resulting in energy deficiency and toxic acumulation in the patient’s body. Typical clinical symtoms of FAODS include rhabdomyolysis, myoglobinuria, cardiomyopathy, hypoketotic hypoglycemia and liver dysfunction on the newborns and could lead to mortality in most of the cases. Mutations occur in different genes in the enzymatic pathway of the mitochrondria may cause diffirent types of FAODS.The objective of this study was to screen and identify genetic mutations associated with fatty acid oxidation disorders in Vietnamese patients through whole exome sequencing analysis. The result revealed a reported homozygous c.199-10T>G mutation in the position of 10 nucleotides before the exon 3 of the SLC25A20 gene. The SLC25A20 gene encodes the carnitine acylcarnitine translocase (CACT), which plays an important role in transporting acylcarnitine and carnitine in the mitochondria. Genetic mutations in this gene often lead to carnitine-acylcarnitine translocase deficiency (CACTD) - a rare form of FAODs. By in silico analysis, the c.199-10T>G mutation was predicted as a splite site mutation that could lead to exon skipping during the creation of mature mRNA. Genetic analysis of the patient’s family showed that both parents had the mutation c.199-10T>G in heterozygous form. This result suggests that every mutant allele in the patient is inherited from parents. Our finding not only improved our understanding of the c.199-10T>G mutation in SLC25A20 gene of our patient but also provides important information for future research, diagnosis and genetic counseling of FAOS in Vietnamese patients.

Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic ERCC8 (CS-A) or ERCC6 (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without photosensitivity, which delayed a clinical diagnosis for 16 years. By whole-exome sequencing we identified the two novel compound heterozygous ERCC8 variants c.370_371del (p.L124Efs*15) and c.484G>C (p.G162R). The causality of the ERCC8 variants, of which one results in a frameshift and the other affects the WD3 domain, was tested and confirmed by a rescue experiment investigating DNA repair in H2O2 treated patient fibroblasts. Structural modeling of the p.G162R variant indicates effects on protein-protein interaction. This case shows the importance to test for ERCC6 and ERCC8 variants even if patients do not present with a complete CS phenotype.

Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic

Glycogen storage disease type Ia (GSD Ia), a rare autosomal inherited disorder, is characterized by accumulation of excessive glycogen and fat in the liver. Primary symptoms of GSD Ia include hypoglycemia; metabolic acidosis; elevated levels of lactate, uric acid and lipids; hepatomagaly and growth retardation. Glycogen storage disease type Ia was caused by mutations in the G6PC gene. In this study, mutations in a Vietnamese patient with glycogen storage disease type Ia were analyzed using the whole exome sequencing method. A missense mutation c.356A>T (p.His119Leu) in the G6PC gene of the patient was identified in exon 3. Genetic analysis confirmed that this mutation was present under homozygous form In-silico analyses using SIFT and Mutation Taster confirmed the damaging effects of this mutations on the function of the proteins. This result enriches knowledge of the G6PC gene mutation spectrum and provides genetic data for further studies on glycogen storage disease type Ia in Viet Nam.

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by malfunction of the branched-chain α-ketoacid dehydrogenase complex (BCKDH). This enzyme complex participates in the catalyzing metabolisms of the branched-chain α-ketoacids, the second step of the degradation of branched-chain amino acids. Impaired activities of the BCKAD complex lead to an increase of the levels of branched- chain amino acid such as leucine, valine, and isoleucine in the blood. In children with maple syrup urine disease, catalysis of the metabolisms of some amino acids failed to be implemented, leading to an accumulation of the amino acids which has been shown as one of the causes of neurological complications, intellectual disabilities, and nervous paralysis or even death. Pathogenic mutations normally occur in BCKDHA, BCKDHB, DBT and DLD genes which encode the E1α, E1β, and E2 subunits of the BCKDH complex. In the present study, a homozygous mutation in the BCKDHB gene (c. 1016C>T) in a pediatric patient with MSUD diagnosed at The National Hospital of Pediatrics was identified using whole exome and Sanger sequencing methods. As a result, the inheritance of the homozygous mutation related to MSUD in BCKDHB gene within the pedigree of the patient’s family was determined. The results indicated that the mutation in the BCKDHB gene was inherited from both of the patient’s parents. In addition, this finding provides an important scientific basis to researches on MSUD in the Vietnamese population.

Background: Expanded newborn screening (ENBS) utilizing tandem mass spectrometry (MS/MS) for inborn metabolic diseases (IMDs), such as organic acidemias (OAs), fatty acid oxidation disorders, (FAODs), and amino acid disorders (AAs), is increasingly popular but has not yet been introduced in many Asian countries. This study aimed to determine the incidence rates of OAs, FAODs, and AAs in Asian countries and Germany using selective screening and ENBS records. Materials and methods: Selective screening for IMDs using gas chromatography–mass spectrometry and MS/MS was performed among patients suspected to be afflicted in Asian countries (including Japan, Vietnam, China, and India) between 2000 and 2015, and the results from different countries were compared. Similarly, ENBS results from Japan, South Korea, Taiwan, and Germany were compared. Additionally, the results of selective screening and ENBS in Japan were compared. Results: Among 39,270 patients who underwent selective screening, IMDs were detected in 1170. Methylmalonic acidemia was frequently identified in several countries, including Japan (81/377 diagnosed IMDs), China (94/216 IMDs), and India (72/293 IMDs). In Vietnam, however, β-ketothiolase deficiency was particularly frequent (33/250 IMDs). ENBS yielded differences in overall IMD rates by country: 1:8557 in Japan, 1:7030 in Taiwan, 1:13,205 in South Korea, and 1:2200 in Germany. Frequently discovered diseases included propionic acidemia (PPA) and phenylketonuria (PKU) in Japan, 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) and PKU in Taiwan, MCCD and citrullinemia type I in South Korea, and PKU and medium-chain acyl-CoA dehydrogenase deficiency in Germany. Furthermore, in Japan, selective screening and ENBS yielded respective PPA frequencies of 14.7% and 49.4% among all organic acidemias. Conclusion: The incidence rates of IMDs vary by country. Moreover, the disease spectra of IMDs detected via selective screening differ from those detected via ENBS. Keywords: Organic acidemia, Fatty acid oxidation disorder, Amino acid disorder, Inherited metabolic disease, Expanded newborn screening, Incidence rate

Osteogenesis imperfecta (OI) has not been studied in a Vietnamese population before. The aim of this study was to systematically collect epidemiological information, investigate clinical features and create a clinical database of OI patients in Vietnam for future research and treatment strategy development. Participants underwent clinical and physical examinations; also medical records were reviewed. Genealogical information was collected and family members’ phenotypical manifestations recorded. Cases were classified according to the Sillence classification. In total, 146 OI patients from 120 families were studied: 46 with OI Type I, 46 with Type III and 54 with Type IV. Almost patients had skeletal deformations. One hundred and forty-two had a history of fractures, 117 blue sclera, 89 dentinogenesis imperfecta and 26 hearing loss. The total number of fractures was 1,932. Thirty-four patients had intra-uterine fractures and nine had perinatal fractures. Surgery was performed 163 times in 58 patients; 100 osteosyntheses and 63 osteotomies. Bisphosphonate treatment was used in 37 patients. The number of affected individuals and predominance of severe forms of OI indicate that the disease is under diagnosed in Vietnam, especially in cases without a family history or with mild form of OI. Deformities appeared in all patients with different severity and localisation, affecting mostly the lower limbs. OI medical and surgical treatment rates are low and in most cases surgery was performed due to fractures. Compared to previous studies, our results indicate a lower OI prevalence and greater severity of symptoms in the Vietnamese population when compared with other areas. Further investigation, improved diagnosis and treatment are needed to increase the patients’ quality of life.

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN&rsquo, s activities for children living with CAH in the Asia Pacific. The seven stages of the KTA action cycle inform a systematic examination of comprehensive, collaborative, sustained actions to address a complex health challenge. The KTA framework demonstrates the &ldquo, how&rdquo, of CLAN&rsquo, s approach to knowledge creation and exchange, and the centrality of community development to multisectoral collaborative action across a range of conditions, cultures and countries to redressing child health inequities. This includes a commitment to: affordable access to essential medicines and equipment, education, research and advocacy, optimisation of medical management, encouragement of family support groups, efforts to reduce financial burdens, and ethical, transparent program management as critical components of success. Improvements in quality of life and health outcomes are achievable for children living with CAH and other chronic health conditions in resource-poor settings. CLAN&rsquo, s strategic framework for action offers a model for those committed to #LeaveNoChildBehind.

We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice.

Glycosaminoglycans (GAGs) are accumulated in various organs in both mucopolysaccharidoses (MPS) and mucolipidoses II and III (ML II and III). MPS and ML II and III patients can not properly degrade dermatan sulfate (DS) and/or heparan sulfate (HS). HS storage occurs in the brain leading to neurological signs while DS storage involves mainly visceral and skeletal manifestations. Excessive DS and HS released into circulation and thus blood levels of both are elevated, therefore, DS and HS in blood could be critical biomarkers for MPS and ML. Such measurement can provide a potential early screening, assessment of the clinical course and efficacy of therapies. We here assay DS and HS levels in MPS and ML patients using liquid chromatography tandem mass spectrometry (LC/MS/MS). Plasma samples were digested by heparitinase and chondroitinase B to obtain disaccharides of DS and HS, followed by LC/MS/MS analysis. One hundred-twenty samples from patients and 112 control samples were analyzed. We found that all MPS I, II, III and VI patients had a significant elevation of all DS+HS compositions analyzed in plasma, compared with the controls (P

Background: The SMN1 gene is now recognized as a spinal muscular atrophy (SMA)-causing gene, while SMN2 and NAIP have been characterized as a modifying factor of the clinical severity of SMA. Gene dosage of SMN2 is associated with clinical severity of SMA. But the relationship between gene dosage of NAIP and clinical severity of SMA remains to be clarified, although complete deletion of NAIP is frequent in type I patients. Methods: To evaluate the contribution of the SMN2 and NAIP gene dosages to SMA, quantitative real-time polymerase chain reaction was used to measure copy numbers of SMN2 and NAIP in 34 Vietnamese SMA patients lacking SMN1 (13 type I, 11 type II and 10 type III patients). Results: The SMN2 copy number in type I patients was significantly lower than that in type II–III patients, which was compatible with the previous reports. In contrast, 25 out of 34 patients had only zero or one copy of NAIP, while 50 out of 52 controls had two or more copies. For NAIP (+) genotype, six out of 13 type I patients, eight out of 11 type II patients and six out of 10 type III patients carried one NAIP copy. Conclusions: The SMN2 copy number was related to the clinical severity of SMA among Vietnamese patients. The presence of one NAIP copy, that is, heterozygous NAIP deletion, was common in Vietnamese SMA, regardless of clinical phenotype.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), required for degradation of keratan sulfate and chondroitin-6-sulfate. In order to study the effects of a missense mutation in the active site cysteine in the GALNS gene that is conserved in all mammalian sulfatases, we produced a p.C76S (an active site replacement) knock-in mouse by replacing the Cys76 with Ser in the endogenous murine Galns by targeted mutagenesis. Homozygous Galns tm(C76S)slu mice had no detectable GALNS enzyme activity. At age of 2–4 months, lysosomal storage was present primarily within reticuloendothelial cells such as Kupffer cells and spleen sinusoidal lining cells. Vacuolar change was present in glomerular visceral epithelial cells and was not present in hepatocytes or renal tubular cells. In the brain, hippocampal and neocortical neurons and meningeal cells showed lysosomal storage. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, the Galns tm(C76S)slu mice had visceral storage of GAGs in organs but lacked the skeletal features of human MPS IVA. In contrast to a previously reported transgenic model ( Galns tm(hC79S·mC76S)slu ), in which the inactive human GALNS transgene was overexpressed, no reduction in other sulfatases was observed. In addition, the Galns tm(C76S)slu mice displayed milder storage. We conclude that the milder phenotype is characteristic of isolated GALNS deficiency while the more severe phenotype reflected in the Galns tm(hC79S·mC76S)slu mice was due to deficiency of other sulfatases caused by oversaturation of the sulfate modifying enzyme by the inactive human gene product.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The aims of this study were to establish Chinese hamster ovary (CHO) cells overexpressing recombinant human GALNS (rhGALNS) and to assess pharmacokinetics and tissue distribution of purified enzymes by using MPS IVA knock-out mouse (Galns(-/-)). The CHO-cell derived rhGALNS was purified from the media by a two-step affinity chromatography procedure. The rhGALNS was administered intravenously to 3-month-old Galns(-/-) mice at a single dose of 250U/g of body weight. The treated mice were examined by assaying the GALNS activity at baseline and up to 240min to assess clearance of the enzyme from blood circulation. The mice were sacrificed 4h after infusion of the enzyme to study the enzyme distribution in tissues. The rhGALNS was purified 1317-fold with 71% yield. The enzyme was taken up by Galns(-/-) chondrocytes (150U/mg/15h). The uptake was inhibited by mannose-6-phosphate. The enzyme activity disappeared from circulation with a half-life of 2.9min. After enzyme infusion, the enzyme was taken up and detected in multiple tissues (40.7% of total infused enzymes in liver). Twenty-four hours after a single infusion of the fluorescence-labeled enzymes into MPS IVA mice, biodistribution pattern showed the amount of tagged enzyme retained in bone, bone marrow, liver, spleen, kidney, and heart. In conclusion, we have shown that the phosphorylated rhGALNS is delivered to multiple tissues, including bone, and that it functions bioactively in Galns(-/-) chondrocytes implying a potential enzyme replacement treatment.

The National Hospital of Pediatrics (NHP), Hanoi, Vietnam is an 1200 bed tertiary referral centre servicing approximately 30 million people from northern provinces of Vietnam. This audit was undertaken to analyze anecdotal reports of increasing patient numbers. Retrospective review of all CAH patients registered at NHP from 1999- 5.2014. Ethical clearance was granted by the NHP Directorate. At the start of 1999 there were 90 children with CAH managed at NHP. By May 2014 this increased to 715 including 375 (52%) male patients and 340 (48%) female patients. Number of cases with 21α-hydroxylase deficiency (21-OHD), 11β-hydroxylase deficiency and 3β-hydroxysteroid dehydrogenase deficiency was 703 (98.3%); 9 (1.3%) and 3 (0.4%), respectively. Among cases with 21-OHD, 72% were salt wasting and 28% were simple virilisation). Total number of cases representing a more than seven fold increase over 14 years. Number of new cases doubled from 30 to 67 in 2013. Most children (85%) were diagnosed at less than 12 months of age (55% at less than 1 month of age); 70% of all children were younger than 10 years. Formal mortality figures were low (7 known deaths). The caseload of CAH at NHP has increased since 1999 and additional capacity is needed for patient care. Introduction of NBS would enable more accurate estimation of CAH incidence, reduce infant mortality and minimize trauma to affected infants and their families.

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders, each of which involves a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both. Classic CAH is rare, about 1 case per 16,000 population. However CAH with cholestatic jaundice is extremely rare. A 23 days old boy presented with vomiting, persistent jaundice. He was born at term, and his birth weight was 3 kg. In family history, no liver or endocrine disease was reported. On examination, his weight was 3 kg; his height was 51 cm; jaundice, hyperpigmentation, dehydration, no hepatomegaly. Strength of his pennis was 3 cm; 2 testis were in the scrostum with volume of 1 ml. Investigation showed : electrolyte imbalance Na+ 110 mmol/l, K+ 7.3 mmol/l, Cl- 80mmol/l, 17 OHP 111 ng/ml, Testosteron 36.36 nmol/l, cholestatic jaundice : total bilirubin 114.6 mcmol/l, direct bilirubin 75.5 mcmol/l,GOT 40 UI/l, GPT 25UI/l, GGT 142.76 UI/l. The markers for viral hepatitis were negative. Abdominal ultrasound was normal. He was diagnosed of CAH and treated with hydrocortisone and fludrocortisone. After 1 month of treatment, jaundice disappears and electrolyte is normalized Written informed consent was obtained from the patient for publication of this Case report (and any accompanying images). A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Patients and methods From 2007 to 2013, 30 children with primary hyperlipidemia were recruited and were treated with diet and/or lipid-lowering drug therapy at the National Hospital of Pediatrics, Hanoi, Vietnam. Clinical symptoms and biochemical finding, outcome of treatment were studied. Results: Among 30 cases from 28 families, 8 patients were mixed hyperlipidemia (MHL), 13 patients were hypertriglyceridemia (HT) and 9 patients were hypercholesterolemia (HC). Mean age of diagnosis was 5.5 years (1 month – 16 years). The rate of male/female was 13/17. Clinical manifestations included hepatomegaly (4 cases), xanthemas in the knees and elbows (5 cases), “creamy” blood (21 cases). Twenty cases were clinical asymptomatic. 8/28 patients had family history with hyperlipidemia and cardiovascular diseases. Serum cholesterol levels of HC group was 9.2 ± 4 mmol/l. Serum triglyceride level of HT group was 23.6 ± 9.9 mmol/l. MHL group had hypercholesterolemia (12.1 ± 4.5 mmol/l) and hypertriglyceridemia (20.3 ± 10.5 mmol/l). After interventions, HT group had the best outcome with serum triglyceride level was 10.1 ± 4.6 mmol/l, next to MHL group with serum cholesterole level was 5.8 ± 1.8 mmol/l, and serum triglyceride level was 9.5 ± 5.2 mmol/l; finally, serum cholesterole level of HC group was 12.4 ± 5.5 mmol/l. Five infants with HT had the best outcome of treatment: serum triglyceride level decreased from 19 57.6 mmol/l to 5 10 mmol/l. Two patients with HC had the worsen results (unchanged blood lipid level).

Adrenocortical carcinoma is rarely seen in a neonatal period. Adrenocortical carcinoma usually causes virilisation, precocious puberty, Cushingoid syndrome.

Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic β-cells. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2). Severe forms of congenital HH are caused by inactivating mutations in ABCC8 and KCNJ11, which encode the two components of the pancreatic β-cell ATP-sensitive potassium channel. Our aim is to identify mutations in the ABCC8 and KCNJ11, HNF4A and GLUD genes, and to describe genotype and phenotype correlations of Vietnamese children with congenital hyperinsulinism. A prospective study was conducted on 65 cases with congenital hyperinsulinism diagnosed and treated at the National Hospital of Pediatric from January 2007 to April 2014. Patients were selected by using inclusion criteria of Hussain K (2008). Mutations were identified in 32 cases (49.2%) including mutations of ABCC8 gene (28 cases; 43.1%), KCNJ11 (3 cases; 4.6%), HNF4A (1 case; 1.5%). 100% of cases with homozygous/compound heterozygous recessive mutations or one paternal dominant mutation of ABCC8 gene did not respond to diazoxide treatment and required 95% pancreatectomy. Molecular analysis using pancreas tissue after surgery from cases with one mutation of ABCC8 gene inherited from father confirmed focal lesion type. Other cases without identified mutations usually responded to diazoxide. In conclusions, children with congenital hyperinsulinism should be performed mutation analysis which helps in making diagnosis and treatment decision. Families of children with congenital hyperinsulinism should be given genetic counseling. Prenatal diagnosis should be performed as well as follow - up and treatment should be given to children with congenital hyperinsulinism immediately after birth.

Congenital adrenal hyperplasia (CAH) is one of the most common metabolic diseases. It is caused by a severe or partial impairment of adrenal steroidogenesis affecting cortisol biosynthesis. Approximately 5–8% of all cases are due to steroid 11β-hydroxylase deficiency (11OHD; OMIM +202010), which occurs in approximately 1:100,000 to 1:200,000 live births in non consanguineous populations. Mutations in the CYP11B1 gene, causing 11b-hydroxylase deficiency in the zona fasciculate in the adrenal cortex, have been identified. Our aim is to describe clinical and biochemical features in patients with CAH due to 11β-hydroxylase deficiency. The case series report included 9 patients (6 male and 3 female) from 7 unrelated families who was identified novel and/or reported homozygous or compound heterozygous mutations in CYP11B1 gene. Diagnosed age was from 2 to 11 years old. All three female cases presented with ambiguous genitalia at birth. Other clinical features were hypertension (6/7 cases); hyperpigmentation (5/7 cases); pseudo-precocious puberty (male) (5/5 cases). Hypokalemia was noted in 3/7 cases. Three cases need antihypertensive drug associated with hydrocortisone replacement therapy. In conclusions, the clinical hallmark of 11β hydroxylase deficiency is variable and virilization and hypertension are the prominent clinical features of 11b hydroxylase deficiency. Biochemical identification of elevated precursor metabolites is not usually available and mutation analysis of CYP11B1 will held confirmation of diagnosis.

Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1 (HNF-1β) gene, mostly generating truncated protein. Various phenotypes are related to HNF-1β mutations. Our aim to describe clinical and genetic findings in the unreported Vietnamese case identified with HNF-1β mutations. The proband with kidney failure from 7.5 years of age and diabetes diagnosed at 13.5 years of age who were described. Case report included information: characteristics of diabetes, renal function and structure, pancreas structure. Genomic DNA were extracted from WBC of whole blood and HNF-1β mutation was performed using PCR and direct sequencing. The proband is heterozygous for a novel HNF1B missense mutation (c.505T>C; p.Y169H). This mutation results in the substitution of the amino acid histidine (charged polar) for tyrosine (uncharged polar) at codon 169. The tyrosine residue is conserved across species and it is therefore likely that the p.Y169H mutation is pathogenic. This result is consistent with a diagnosis of renal cysts and diabetes syndrome (RCAD). Testing was done for proband's parents and no mutation was found in HNF1B. It is therefore likely that the p.Y169H mutation has arisen de novo. Kidney MRI showed right kidney atrophy and pancreas MRI showed only tissue of head of pancreas. Investigations at 14.5 years of age – diagnosed diabetes showed: plasma urea 10.1 mmol/l; creatinine 250 micrommol/l; HbA1C 13.6%. He was given insulin of 0.8 UI/Kg/day and HbA1C was 6.8% after one year of treatment with insulin injection. Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1β is warranted, even without a family history of diabetes, in non obese patients with diabetes and slowly progressive non diabetic nephropathy, particularly when pancreatic atrophy. Written informed consent was obtained from the patient for publication of this Case report (and any accompanying images). A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required. Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life. This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs.

Deficiency of 21-hydroxylase (21-OHD) is present in 90–95% cases of congenital adrenal hyperplasia (CAH), an autosomal recessive disorder. CAH affects severely on the physical development and reproductive function. In monitoring the disease and evaluating treatment outcome, presentation of salt wasting, electrolyte disturbance, androgenism, cushingoid features, plasma levels of 17-OHP, testosterone, Δ4-androstenedione, urinary levels of 17-OHCS, 17-CS, and bone age were used. We aimed to study relationship between the value of the plasma 17–OHP and the value of the plasma testosterone levels to monitor treatment of CAH. The study was prospective. We collected 82 CAH Vietnamese patients who were diagnosed of 21-OHD. The have been treated and monitored at the Vietnam National Hospital of Pediatrics. Hanoi, Vietnam in the period of 1/2007- 1/2010. The value of plasma levels of 17-OHP and testosterone were measured in combination with clinical symptoms every 6 months. In 82 study’s CAH patients aged 1-15 years old, the group aged < 10 years old occupied 82.9%. The salt – wasting form occupied 75.6%; the simple virilizing form 24.4%. 59/82 of patients (71.1%) had successful treatment with the mean plasma level 17-OHP of 0.02-5.67 nmol/l and the mean levels of testosterone of 0.01- 8.02 nmol/l according to groups'ages. The mean levels of plasma 17-OHP and testosterone also increased with age and sex in the group of patients having failed treatment. It confirmed a positive relationship between the value of plasma 17 – OHP and levels of the testosterone with 95% significant confidence. Each time of patient examination, besides clinical symptoms and plasma levels of 17-OHP should be done to evaluate treatment.

Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It includes a group of autosomal recessive disorders caused by the deficiency of one of the enzymes involed in one of the various steps of adrenal steroid synthesis. The most common form of CAH (95%) is caused by mutations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme (P450c21). Two major phenotype are recognized in 21-OHD: classic and non-classic. Classic CAH is clinically categorized in two groups: the simple-virilising and the salt-wasting form. The National Hospital of Pediatrics (NHP) in Hanoi is an 1100 bed tertiary referral centre servicing approximately 30 million people from northern provinces of Vietnam. At the start of 1999 there were 91 children with CAH due to 21-hydroxylase deficiency (21-OHD) managed at NHP. By June 2012 this increased to 624 [98.2% due to 21-OHD], representing a more than six fold increase over 12 years. Number of new cases ranged from 40 to 70 per year. We aim to determine the mutations in the CYP21A2 gene in Vietnamese patients with CAH and attempt a genotype-phenotype correlation. Molecular analysis was performed using PCR, multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 81 CAH patients (39 male and 42 female). Correlation between phenotype and genotype was evaluated based on identified mutations and clinical manifestations. Mutations were identified in 92.6% mutant alleles, 22 genotypes were found in 81 cases. Seven different causative mutations were identified in CYP21A2 including one novel mutation. The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (54 alleles; 36%) mutation, followed by Large lesion (42 alleles; 28%) including exon 1 deletion (2 alleles), exon 1-3 deletion (10 alleles), exon 1-6 deletion (4 alleles), exon 1-8 deletion (2 alleles) and larger deletion (24 alleles); p.R356W (26 alleles; 17.3%); p.l172N (15 alleles; 10%). The rarer mutations were novel one p.R484fsX541 (6 alleles; 4%); p.Q318X (4 alleles; 2.7%) and p.R426C (3 alleles; 2%). The majority of patients (61 cases; 75.3%) were homozygotes. Four cases were compound heterozygous. Thirteen patients had only a heterozygous mutation detected. Genotype accurately predicted phenotype in 93.8 and 100% of patients with salt-wasting and simple virilizing, respectively. The spectrum of mutations of the CYP21A2 gene in Vietnamese patients is comparable to the some reported in other Asian population. Large deletion accounts for nearly one-third of the genetic defects. Therefore, laboratory should include methods for detecting point mutations as well as large deletions. Genotype-Phenotype correlation was high in the studied patients.

Osteogenesis Imperfecta (OI) is a heterogeneous genetic disorder, with features that include increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide from children with few fractures and normal stature to children with multiple fractures, long bone deformity, scoliosis and extreme short stature. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. We aim to evaluate the effect of OI on the well being of children with the disorder and their families through a family-centered questionnaire. Sixty children with OI from the Vietnam National Hospital of Pediatrics and/or their parent(s), who attended the first annual family support group in 2011, completed a child and parent questionnaire. 60 patients participated, 26 female and 34 male. The median age was 6.0 years [interquartile range (IQR) 0.25 - 18 years]. Of these, 36 (60%) had dentinogenesis imperfect and 23 (38.3%) had a scoliosis. The median number of fractures was 6.0 (IQR 0 – 30) and median number of hospitalizations due to OI was 5.0 (IQR 0-30). Among patients of school age, 9 (15%) could not go to school due to OI. Almost all parents (93.7%) worried about school social communication of the patients. Among these parents, 100% fear of inferiority with friends and 98.3% fear of broken bones. Most parents (76.2%) were significantly concerned about their child's health. The parents’ themselves reported psychological concerns, with feelings of desperation (58.4%), anxiety (81.7%) and depression (56.7%). Osteogenesis imperfecta appeared to have a significant deleterious effects on the life of the patients and their families. These data provide a baseline from which to evaluate the effectiveness of interventions to improve the medical and psychological needs of this cohort and their families.

Androgen insensitivity syndrome (AIS) is the most common specific cause of 46,XY disorder in sex development. The androgen signaling pathway is complex but so far, the only gene linked with AIS is the androgen receptor (AR). Mutations in the AR are found in most subjects with complete AIS but in partial AIS, the rate has varied 28–73%, depending on the case selection. More than over 800 entries of mutations causing AIS, representing over 500 different AR mutations from more than 850 patients with AIS have been reported. We aim to describe clinical manifestations and to identify mutation of AR in Vietnamese patients with AIS. This case series study included 12 patients from 9 unrelated families with AIS. The gonadal position and external genitalia were evaluated clinicaly and using ultrasound. The mutation analysis of AR was performed using PCR and direct sequencing. The age of diagnosis was 1 to 83 years old. 8/12 cases were complete androgen insensitivity syndrome (CAIS) (female external genitalia) and 4 cases were predominantly female partial AIS phenotype. Four cases had two labial testes, six cases had inguinal testes and 2 cases had abdominal testes. Five different mutations of AR were identified from 7 cases of 3 unrelated families including three novel ones. The novel missense mutation p.L701F (c.2103G>T) was identified in a patient of 83 year of age. The novel missense mutation p.L705F (c.2113C>T) was identified in two sibs. The novel mutation p. W752S (c. 2256 G>T) was identified in a child with CAIS phenotype and had family history. The reported missense mutation p.V747M was identified in two sibs. The reported mutation p.V867M (c.2599 G>A) was identified in a child with female phenotype. Our study identified three novel and two reported mutation in the AR gene that may provide us new insights into the molecular mechanisms of AIS. The expanded database of these mutations should benefit patients in the diagnosis and treatment of this syndrome.