Maple Syrup Urine Disease

Disease characteristics
Maple Syrup Urine Disease is caused by a deficiency of the metabolic enzyme branched-chain α-keto acid dehydrogenase (BCKDH), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products in the blood and urine.

Prevalence
Maple Syrup Urine Disease is quite rare (1:180,000 infants) yet its carrier frequency in Ashkenazi Jewish population could be as high as 1:80 individuals. It is also quite prevalent in Amish and Mennonite populations.

Mutation
Four common mutations in enzyme BCKDH can cause MSUD. These mutations occur at positions 183 (R183P), 278 (G278S) 372 (E372X), and  438 (Y438N) amino acid sequence of this enzyme.

Testing criteria and symptoms
Being of Ashkenazi Jewish ancestry
Sweet-smelling urine, with an odor similar to that of maple syrup,
Poor feeding, vomiting, dehydration, lethargy, hypotonia, seizures, ketoacidosis, and neurological decline.