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Thiamine-responsive maple syrup urine disease
Thiamine-responsive maple syrup urine disease (thiamine-responsive MSUD) is a less severe variant of MSUD (see this term) that manifests with a phenotype similar to intermediate MSUD (see this term) but that responds positively to treatment with thiamine.
ORPHA:268184Classification level: Subtype of disorder
- Thiamine-responsive BCKD deficiency
- Thiamine-responsive MSUD
- Thiamine-responsive branched-chain alpha-ketoacid dehydrogenase deficiency
- Prevalence: Unknown
- Inheritance: Autosomal recessive
- Age of onset: Infancy
- ICD-10: E71.0
- OMIM: 248600
- UMLS: C0751285
- MeSH: -
- GARD: -
- MedDRA: -
MSUD has an estimated incidence of 1/150,000 live births. The thiamine-responsive type appears to be very rare.
Thiamine-responsive MSUD is poorly characterized. It appears to usually present after infancy with a phenotype very similar to that seen in intermediate MSUD (see this term). Manifestations include feeding problems, poor growth, maple syrup odor in urine and developmental delay. Older children usually present with learning difficulties. Like classic MSUD (see this term), physiological stress can result in acute decompensation with anorexia, nausea, vomiting (at all ages), ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute / focal dystonia and choreoathetosis (in adults) that can progress to stupor, coma and cerebral edema, if untreated. Thiamine (doses of 10-1000 mg per day) has improved the leucine tolerance in the few reported cases of this MSUD subtype, but some dietary branched-chain amino-acid (BCAA) restriction remains necessary.
MSUD is due to mutations in the genes encoding 3 of the 4 subunits of branched-chain 2-ketoacid dehydrogenase (BCKAD) complex. The genes are BCKDHA (19q13.1-q13.2), encoding E1a; BCKDHB (6q14.1), encoding E1b; and DBT (1p31), encoding E2 respectively. Mutations lead to an accumulation of BCAAs (especially leucine) and branched-chain alpha-ketoacids. In thiamine-responsive MSUD, mutations in DBT predominate.
Inheritance is autosomal recessive and genetic counseling is possible.
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