Overview
Definition
An autosomal recessive metabolic disorder characterized by deficiency of the branched-chain alpha-keto acid dehydrogenase complex, leading to toxic accumulation of leucine, isoleucine, and valine.
Epidemiology
Prevalence ~1 in 185,000 live births globally. High incidence in Mennonite populations.
Etiology & Risk Factors
- BCKDHA, BCKDHB, or DBT gene mutations
- Defective branched-chain amino acid degradation
Clinical Symptoms
- Maple syrup odor in urine and sweat
- Poor feeding and vomiting in infants
- Progressive neurological decline / Lethargy
- Spasticity and seizures
Clinical Approach
Diagnosis
- Elevated plasma branched-chain amino acids (leucine, isoleucine, valine)
- Presence of alloisoleucine in plasma (pathognomonic)
- Genetic testing
Management
- Strict dietary restriction of branched-chain amino acids (special formulas)
- Thiamine supplementation (in thiamine-responsive forms)
- Liver transplantation (curative for metabolic crisis risk)
Complications
- Severe brain edema
- Irreversible intellectual disability
- Metabolic coma / Death during illness catabolism