Maple Syrup Urine Disease

Maple syrup urine disease (MSUD), which affects about 5 per million births, is caused by a defective enzyme involved in metabolising the branch-chain amino acids. It leads to mental retardation and early death if untreated, but patients who are identified at birth can live a nearly normal life if they follow a special diet. MSUD type 1B is more than twice as common in Ashkenazi Jews as in the general population. Type 1A is more common in Old Order Mennonites.

MSUD is an autosomal recessive disorder that can be caused by a defect in various genes:

• BCKDHA OMIM 608348.0001
• BCKDHB OMIM 248611
• DBT OMIM 248610
• DLD OMIM 238331

The following SNPs may be involved:

• rs12021720
• rs17856511
• rs28934895, also known as R183P (the most common SNP in Ashkenazi Jews); the risk genotype is CC
• rs28940288

23andMe tests for two mutations using their own terminology:

• i3002808, which is equivalent to rs28934895
• i4000422, also known as G278S (risk genotype AA)