Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease caused by a defect in the alpha-keto acid dehydrogenase complex (BCKAD complex), which mediates the breakdown of the branched-chain amino acids leucine, isoleucine, and valine. The defect results in the accumulation of branched-chain amino acids. The disease is rare, with an incidence of approximately 1:150,000, and is caused by pathogenic variants in the BCKDHA, BCKDHB, and DBT genes, which encode three of the four enzymatically active subunits of the BCKAD complex. BCKDHA codes for the E1a subunit, BCKDHB for E1b, and DBT for the E2 subunit.
Depending on the variant, a distinction is made between
- Type Ia (BCKDHA gene)
- type Ib (BCKDHB gene)
- type II (DBT gene)
Clinical symptoms appear already in the first weeks of life and the early childhood years, depending on the form. The classic form of maple syrup disease manifests in the first weeks of life with nonspecific symptoms (weakness in drinking, vomiting, comatose states, cerebral edema). The intermediate form is often associated with developmental delay. Acute metabolic derailments may occur during catabolic stress. The patients' urine has a characteristic odor.
Diagnosis of maple syrup disease is part of newborn screening. If positive, the diagnosis can be confirmed by molecular genetics. Due to the possibility of early detection and therapy with appropriate diet, the prognosis of the disease is favorable.
Frazier et al. 2014, Mol Genet Metab 112(3):210 / Strauss et al., GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019