BCKDHB Research Articles

Two Novel Mutations in the BCKDHB Gene Cause Intermediate Maple Syrup Urine Disease.

Two Novel Mutations in the BCKDHB Gene Cause Intermediate Maple Syrup Urine Disease.

Maple syrup urine disease diagnosis in Brazilian patients by massive parallel sequencing

Biallelic pathogenic variants cause maple syrup urine disease (MSUD) in one of the branched-chain α-keto acid dehydrogenase (BCKDH) complex genes (BCKDHA, BCKDHB, DBT, DLD, and PPM1K) leading to the accumulation of leucine, isoleucine, and valine. This study aimed to perform a molecular diagnosis of Brazilian patients with MSUD using gene panels and massive parallel sequencing. Eighteen Brazilian patients with a biochemical diagnosis of MSUD were analyzed by massive parallel sequencing in the Ion PGM Torrent Server using a gene panel with the BCKDHA, BCKDHB, and DBT genes. The American College of Medical Genetics and Genomics guidelines were used to determine variant pathogenicity. Thirteen patients had both variants found by massive parallel sequencing, whereas 3 patients had only one variant found. In 2 patients, the variants were not found by this analysis. These 5 patients required additional Sanger sequencing to confirm their genotype. Twenty-five pathogenic variants were identified in the 3 MSUD-related genes (BCKDHA, BCKDHB, and DBT). Most variants were present in the BCKDHB gene, and no common variants were found. Nine novel variants were observed: c.922 A > G, c.964C > A, and c.1237 T > C in the BCKDHA gene; and c.80_90dup, c.384delA, c.478 A > T, c.528C > G, c.977 T > C, and c.1039-2 A > G in the BCKDHB gene. All novel variants were classified as pathogenic. Molecular modeling of the novel variants indicated that the binding of monomers was affected in the BCKDH complex tetramer, which could lead to a change in the stability and activity of the enzyme. Massive parallel sequencing with targeted gene panels seems to be a cost-effective method that can provide a molecular diagnosis of MSUD.

Genotypic and Phenotypic Spectrum of maple syrup urine disease in Zhejiang of China.

Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB, and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated. Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD. Retrospective population-based cohort. We analyzed 20 MSUD patients from the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to May 2023. Patients' blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability, and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect. We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing. This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.

Identification of genes in a genomic DNA sequence

Today, newer pyrosequencing methods have drastically cut the cost of sequencing and may eventually allow every person the possibility of personalized genome information. Being able to read how our genes are expressed offers the promise of advanced medical treatments, but it will certainly require considerable work to generate, understand, organize, and apply this massive amount of data to human disease. This study describes the results of the CFTR, MEFV, GALT, PAH, BCKDHB and DBT genes analysis of Azerbaijanian patients. The molecular diagnostics methods using specific primers to identify CFTR, MEFV, GALT, PAH, BCKDHB and DBT genes many mutations. A total 15 different mutations (R261Q, V245V, P281L, R241C, L385L, V399V, E280K, R261X, A434D, R176X, Ex6-96A> G, R241C, R243Q, R252Q, Y356X) and 2 different polymorphisms (Q232Q,V245V) were detected of the PAH gene. 4 different mutations (P325L, H132Q, Q334K, N314D ) were detected of the GALT gene, 6 different mutations (Phe508del, Phe508del/5T, R117H/R334W, R553X and 965 (T-C)) were found in the CFTR gene, polymorphisms (D102D, G138G, A165A, R202Q, R314R, G474G, G476G, D510D) were detected of the MEFV gene, 2 different mutations were found of the BCKDHB gene and one mutation detected of the DBT gene in patients from Azerbaijani population. To prophylaxis the phenylketonuria, galactosemia, maple syrup urine disease, cystic fibrosis disease and Fammilian Mediterranian Fever it is recommended to screen genetically newborns, to consult medical-genetically risky families, and to carry out prenatal diagnostics during pregnancies for those families.

Newborn screening of maple syrup urine disease and the effect of early diagnosis

BackgroundMaple syrup urine disease (MSUD) is a rare disease for which newborn screening (NBS) is feasible but not universally applied in China. We shared our experiences with MSUD NBS. MethodsTandem mass spectrometry-based NBS for MSUD was implemented in January 2003, and diagnostic methods included urine organic acid analysis via gas chromatography–mass spectrometry and genetic analysis. ResultsSix MSUD patients were identified from 1.3 million newborns, yielding an incidence of 1:219,472, in Shanghai, China. The areas under the curve (AUCs) of total leucine (Xle), Xle/phenylalanine ratio, and Xle/alanine ratio were all 1.000. Some amino acid and acylcarnitine concentrations were markedly low in MSUD patients. 47 MSUD patients identified here and in other centers were investigated, which included 14 patients identified by NBS and 33 patients diagnosed clinically. Forty-four patients were subclassified into classic (n = 29), intermediate (n = 11) and intermittent (n = 4) subtypes. Due to earlier diagnosis and treatment, screened classic patients showed a higher survival rate (62.5%, 5/8) than clinically diagnosed classic patients (5.2%, 1/19). Overall, 56.8% (25/44) of MSUD patients and 77.8% (21/27) of classic patients carried variants in the BCKDHB gene. Among 61 identified genetic variants, 16 novel variants were identified. ConclusionMSUD NBS in Shanghai, China, enabled earlier detection and increased survivorship in the screened population.

Teaching NeuroImages: When MRI is a clue in episodic ataxia

A 3-year-old girl presented with episodic ataxia for the past month. It lasted for 1–2 days continuously after a febrile illness. MRI was suggestive of a neurometabolic disorder (figure, A–L). Plasma valine and leucine and urinary branched-chain aminoacids were elevated. Clinical exome revealed a homozygous, missense, pathogenic variation in BCKDHB gene (exon 5, chr6:80878686A>C; p.His191Pro).

Identification of a novel homozygous mutation of the BCKDHB gene in an Iranian patient with maple syrup disease using next-generation sequencing

BackgroundMaple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased branched-chain alpha-keto acid dehydrogenase (BCKD) activity in human tissues. The BCKD enzyme is mostly active in the human body in the muscles and the brain; thus, genetic deficiency of the BCKD complex can result in neurological damage in patients. Deleterious mutations in BCKDHB, BCKDHA, DBT, and DLD genes have a significant impact on BCKD activity. MethodsIn this study, we described a case of MSUD in a consanguineous Iranian family without a history of metabolic disorders. A 7-year-old boy was diagnosed 21 days after birth with lethargy, feeding problems, and vomiting. Plasma amino acid concentration and level of ammonia were measured. And then, whole-exome sequencing (WES) 100× was used to identify causative mutation along with some bioinformatics analysis. ResultsA novel pathogenic homozygous mutation, c.552_553insA; P185Tfs*17, was detected in the BCKDHB gene's exon5. This variant was predicted as a pathogenic mutation using bioinformatics tools including Mutationtaster, Fathmm-mkl, Provean, DEOGEN2, SNPs&GO, PhyloP, and PhastCons. This mutation leads to a truncated protein in which conserved regions are lost. Besides, the variant is completely co-segregated with the disease in this family. ConclusionA novel pathogenic mutation c.552_553insA in the BCKDHB gene related to MSUD was diagnosed in an Iranian family. This finding from the present study can be efficient in upgrading mutation databases and recognizing MSUD causes.

Successful treatment of severe MSUD in Bckdhb-/- mice with neonatal AAV gene therapy.

Maple syrup urine disease (MSUD) is rare autosomal recessive metabolic disorder caused by the dysfunction of the mitochondrial branched-chain 2-ketoacid dehydrogenase (BCKD) enzyme complex leading to massive accumulation of branched-chain amino acids and 2-keto acids. MSUD management, based on a life-long strict protein restriction with nontoxic amino acids oral supplementation represents an unmet need as it is associated with a poor quality of life, and does not fully protect from acute life-threatening decompensations or long-term neuropsychiatric complications. Orthotopic liver transplantation is a beneficial therapeutic option, which shows that restoration of only a fraction of whole-body BCKD enzyme activity is therapeutic. MSUD is thus an ideal target for gene therapy. We and others have tested AAV gene therapy in mice for two of the three genes involved in MSUD, BCKDHA and DBT. In this study, we developed a similar approach for the third MSUD gene, BCKDHB. We performed the first characterization of a Bckdhb-/- mouse model, which recapitulates the severe human phenotype of MSUD with early-neonatal symptoms leading to death during the first week of life with massive accumulation of MSUD biomarkers. Based on our previous experience in Bckdha-/- mice, we designed a transgene carrying the human BCKDHB gene under the control of a ubiquitous EF1α promoter, encapsidated in an AAV8 capsid. Injection in neonatal Bckdhb-/- mice at 1014 vg/kg achieved long-term rescue of the severe MSUD phenotype of Bckdhb-/- mice. These data further validate the efficacy of gene therapy for MSUD opening perspectives towards clinical translation.

Identification of gene mutations in six Chinese patients with maple syrup urine disease.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD. Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)-Sanger sequencing technology. Bioinformatics software analyzed the variants' pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins. Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing's results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation. Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD's differential diagnosis, early treatment, and prenatal diagnosis.

Genetic analysis of two Chinese families with maple syrup urine disease

To carry out genetic analysis for 3 children from two Chinese families affected with maple syrup urine disease (MSUD). Target capture - next-generation sequencing and Sanger sequencing were used to detect pathogenic variants associated with MSUD. The proband from family 1 was found to harbor homozygous c.560G>T (p.Gly187Val) variant of the BCKDHB gene (NM_000056), whilst the two patients from family 2 were found to harbor compound heterozygous variants c.197-2A>G (splicing)/c.218delT (p.F74Sfs*4) of the BCKDHB gene. Among these, the c.560G>T and c.218delT variants were unreported previously. The new variants discovered in this study have expanded the mutational spectrum of the BCKDHB gene.

Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier.

Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.

Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by deficiency of the branched-chain α-ketoacid dehydrogenase complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. This study presents the clinical and molecular characterizations of four MSUD patients. Clinical data of patients were retrospectively analyzed, and genetic mutations were identified by whole-exome sequencing. CLUSTALX was employed to analyzed cross-species conservation of the mutant amino acid. The impact of the mutations was analyzed with PolyPhen-2 software. The I-TASSER website and PyMOL software were used to predict the protein three-position structure of the novel mutations carried by the patients. Vomiting, irritability, feeding difficulties, seizures, dyspnoea, lethargy and coma were the main clinical presentations of MSUD. Cranial MRI showed abnormal symmetrical signals in accordance with the presentation of inherited metabolic encephalopathy. Seven mutations were detected in four patients, including three novel pathogenic mutations in the BCKDHA (c.656C>A), BCKDHB (deletion of a single-copy of BCKDHB) and DBT (c.1219dup) genes. Structural changes were compatible with the observed phenotypes. Different types of MSUD can display heterogeneous clinical manifestations. Exhaustive molecular studies are necessary for a proper differential diagnosis. The newly identified mutation will play a key role in the prenatal diagnosis of MSUD in the future.

501 Late-Breaking: Search for Genomic Associations with Cryo-resistance of Sperm in Animals

Abstract Genetic resistance to sperm cryopreservation is an important factor in the sires selection. In our study, we studied the cryoresistance of the sperm in Gallus gallus, Bos taurus, Equus ferus caballus. Sperm quality was assessed using computer-assisted semen analysis (CASA). Genetic studies were performed using Affymetrix Axiom®600k Array chips for cocks, Affymetrix Axiom®600k Array for stallions and BovineSNP50 for bulls. For the analysis of genotypes, the GWAS (Genome-Wide Association Studies) was used. The calculations were carried out using the PLINK and EMMAX programs. The candidate genes found as a result of our work were compared with the functions of orthologous genes, according to the publications of other researchers. As a result of comparing different animal species, a common candidate gene was found, localized on chromosome 3 (Gallus gallus) and on BTA9 (Bos taurus) BCKDHB gene encodes the beta subunit E1 of branched chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. In roosters, it was associated with the preservation of sperm motility after cryopreservation, and it was found in the analysis of the integrity of the sperm head in bulls. The functioning of genes associated with meiosis and sperm maturation is an important condition for maintaining its quality after freezing. The work of genes responsible for the formation of membranes and various cellular structures associated with the functions of spermatozoa is also an important factor in cryoresistance. Another important condition for the functioning of the sperm is the expression of genes that prepare the sperm for fertilization. These are calcium metabolism genes involved in preparation for capacitation. Changes in the structure of proteins can lead to premature capacitation and disruption of sperm integrity. The found molecular genetic markers will be used to select sires whose sperm are suitable for freezing. Project of RSF № 18-16-00071.

Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.

Functional assay for analysis of variants of uncertain significance in maple syrup urine disease

Introduction: Enhanced molecular characterisation using high-throughput sequencing has significantly improved patient diagnosis and management. However, the identification of variants of uncertain significance (VUS) limits its use for clinical decision making, such as prenatal diagnosis in subsequent pregnancies. Case report: We report a female infant who presented with mild gross motor delay at 4 months and developed seizures with hypoglycaemia at 5 months. Plasma amino acid and urine organic acid findings were consistent with Maple syrup urine disease (MSUD), despite a normal newborn screening test for this condition. MSUD results in deficiency of branched-chain alpha-ketoacid dehydrogenase, responsible for leucine, isoleucine, and valine degradation, caused by biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT genes. Results: Molecular analysis in this patient identified two VUS, c.434-15_434-4del and c.365A>G (p. Tyr122Cys) in the DBT gene. Functional testing, in the form of leucine decarboxylation studies in fibroblasts revealed deficient function and mRNA splicing studies provided additional data that permitted variant reclassification and subsequent prenatal testing. Conclusion: This case reinforces the need for specialist biochemical genetic laboratories to retain their ability to perform functional assays to aid the resolution of VUS.

Molecular basis of various forms of maple syrup urine disease in Chilean patients

ABSTRACTBackgroundMaple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched‐chain α‐keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients.MethodsThis manuscript describes a cross‐sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.ResultsFour novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients.ConclusionIf MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype‐phenotype relationships more efficiently.

An induced pluripotent stem cell line (SDQLCHi033-A) derived from a patient with maple syrup urine disease type Ib carrying a homozygous mutation in BCKDHB gene.

Maple syrup urine disease (MSUD) type Ib is a subclass of MSUD (248600) which is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex. An induced pluripotent stem cell (iPSC) line was generated from an 11-day-old girl diagnosed with maple syrup urine disease type Ib and carrying a novel homozygous mutation of c.1097C>A (p.P366Q) in BCKDHB gene. This cell line demonstrates a normal karyotype and maintains a pluripotent state, displaying the capability to differentiate into the three germ layer lineages and the absence of exogenous pluripotency vector expression.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity

BackgroundMaple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing.ResultsEight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis.ConclusionGiven that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

Genotype-phenotype correlation of 33 patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.

Hereditary characteristics of the S339L mutation in a patient with maple syrup urine disease in Vietnam

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.