Maple syrup urine disease: The E1{beta} gene of human branched-chain {alpha}-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3{prime} UTR in one of the two E1{beta} mRNAs arises from intronic sequences
- Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
Maple syrup urine disease (MSUD) or branched-chain ketoaciduria is caused by a deficiency in the mitochondrial branched-chain {alpha}-ketoacid dehydrogenase (BCKAD) complex. The clinical manifestations are characterized by accumulation of branched chain amino and {alpha}-ketoacids, which leads to severe cerebral edema with seizures, ketoacidosis, and mental retardation. The BCKAD complex comprises three catalytic components, i.e., a decarboxylase (E1) consisting of two E1{alpha} (M{sub r} = 46,000) and two E1{Beta} (M{sub r} = 37,500) subunits, a transacylase (E2) that contains 24 lipoic acid-bearing subunits, and a dehydrogenase (E3), which is a homodimeric flavoprotein. MSUD is genetically heterogeneous, since mutations in the E1{alpha} subunit (type IA MSUD), the E1{Beta} subunit (type IB), the E2 subunit (type II) and the E3 subunit (type III) have been described. The functional consequences of certain mutations in the BCKAD complex have been studied. 23 refs., 3 figs.
- OSTI ID:
- 446951
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 6 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
AMINO ACID SEQUENCE
DNA SEQUENCING
DNA-CLONING
EXONS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
INTRONS
KETO ACIDS
MENTAL DISORDERS
MESSENGER-RNA
METABOLIC DISEASES
METABOLISM
OXIDOREDUCTASES
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
UROGENITAL SYSTEM DISEASES