Description:
MAPLE SYRUP URINE DISEASE (MSUD), TYPE IA
BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, ALPHA POLYPEPTIDE; BCKDHA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Amino Acid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
3 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| Gene |
BCKDHA |
| Chromosomal Location |
19q13.1-q13.2 |
| Allelic Variant 1 |
608348.0001; MAPLE SYRUP URINE DISEASE, CLASSIC TYPE IA, DUE TO DEFICIENCY OF E1A |
| Identified Mutation |
TYR394ASN; In a classic case of MSUD, Zhang et al. [J Clin Invest 83: 1425 (1989); Mol Biol Med 8: 39 (1991)] identified a T-to-A transversion that altered a tyrosine to an asparagine at residue 394 of the E1-alpha subunit. The father was heterozygous for this mutant allele. The mother was homozygous for the allele encoding the normal tyr394 but expressed only about half of the normal mRNA and protein. The patient was heterozygous for the residue 394 mutation, although only the abnormal allele was expressed as mRNA. Zhang et al. (1989) concluded that the patient was a compound heterozygote, inheriting from the father an allele encoding an abnormal E1-alpha and from the mother an allele containing a cis-acting defect in regulation which abolished the expression of one of the E1-alpha alleles. In cell lines from Mennonite cases of MSUD (GM01655 and GM01099), Matsuda et al. [Biochem Biophys Res Commun 172: 646 (1990)] demonstrated the same tyr394-to-asn mutation resulting from a T-to-A substitution. They noted that although the E1-beta subunit gene is normal, no crossreacting material associated with this gene could be demonstrated, suggesting that the mutation in the E1-alpha gene results in instability of the E1-beta subunit. |
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| Gene |
BCKDHA |
| Chromosomal Location |
19q13.1-q13.2 |
| Allelic Variant 2 |
608348.0001; MAPLE SYRUP URINE DISEASE, CLASSIC TYPE IA, DUE TO DEFICIENCY OF E1A |
| Identified Mutation |
TYR394ASN; In a classic case of MSUD, Zhang et al. [J Clin Invest 83: 1425 (1989); Mol Biol Med 8: 39 (1991)] identified a T-to-A transversion that altered a tyrosine to an asparagine at residue 394 of the E1-alpha subunit. The father was heterozygous for this mutant allele. The mother was homozygous for the allele encoding the normal tyr394 but expressed only about half of the normal mRNA and protein. The patient was heterozygous for the residue 394 mutation, although only the abnormal allele was expressed as mRNA. Zhang et al. (1989) concluded that the patient was a compound heterozygote, inheriting from the father an allele encoding an abnormal E1-alpha and from the mother an allele containing a cis-acting defect in regulation which abolished the expression of one of the E1-alpha alleles. In cell lines from Mennonite cases of MSUD (GM01655 and GM01099), Matsuda et al. [Biochem Biophys Res Commun 172: 646 (1990)] demonstrated the same tyr394-to-asn mutation resulting from a T-to-A substitution. They noted that although the E1-beta subunit gene is normal, no crossreacting material associated with this gene could be demonstrated, suggesting that the mutation in the E1-alpha gene results in instability of the E1-beta subunit. |
| Remarks |
Mennonite; hypotonia; seizures; positive family history; homozygous for a T > A substitution in the E1 alpha subunit of BCKDH (BCKDHA) which changes tyrosine to asparagine at residue 394 of the polypeptide |
| Matsuda I, Nobukuni Y, Mitsubuchi H, Indo Y, Endo F, Asaka J, Harada A, A T-to-A substitution in the E1 alpha subunit gene of the branched- chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients. Biochem Biophys Res Commun172:646-51 1990 |
| PubMed ID: 2241958 |
| dbSNP |
dbSNP ID: 15915 |
| Gene Cards |
BCKDHA |
| Gene Ontology |
GO:0003826 alpha-ketoacid dehydrogenase activity |
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GO:0003863 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity |
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GO:0005739 mitochondrion |
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GO:0005947 alpha-ketoglutarate dehydrogenase complex (sensu Eukarya) |
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GO:0008152 metabolism |
| NCBI Gene |
Gene ID:593 |
| NCBI GTR |
248600 MAPLE SYRUP URINE DISEASE; MSUD |
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608348 BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, ALPHA POLYPEPTIDE; BCKDHA |
| OMIM |
248600 MAPLE SYRUP URINE DISEASE; MSUD |
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608348 BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, ALPHA POLYPEPTIDE; BCKDHA |
| Omim Description |
BCKD DEFICIENCY |
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BCKD, E1-ALPHA SUBUNIT, INCLUDED; BCKDE1A, INCLUDED |
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BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY |
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BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, ALPHA POLYPEPTIDE, INCLUDED;BCKDHA, INCLUDED; BCKDH, INCLUDED |
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BRANCHED-CHAIN KETOACIDURIA |
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KETO ACID DECARBOXYLASE DEFICIENCYTHIAMINE-RESPONSIVE MSUD, INCLUDED |
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MAPLE SYRUP URINE DISEASE, TYPE IA |
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MSUD |
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MSUD, TYPE IA |
| Passage Frozen |
3 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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