Branched-chain ketoaciduria, more commonly known as Maple Syrup Urine Disease (MSUD), is a metabolic disorder which causes toxic buildups of unbroken branched-chain amino acids or keto acids. Passed on autosomal recessively, mutations in specific genes hinder or stop the enzyme complex responsible for normal breakdown of three amino acids found in protein-rich foods from working. The buildup of these toxic keto acids leads to brain damage and eventually death in the affected infant if left untreated (Ogier de Baulny and Saudubray 2002). Although relatively rare in the general population (1/185,000 live births), prevalence in certain ethnic populations are much higher due the founder effect (as high as 1/10). This review will cover the causes, diagnosis/symptoms, genetic prevalence, and ethical issues regarding MSUD.
Causes.
MSUD stems from a disruption of the branched-chain alpha-keto acid dehydrogenase complex. This complex, consisting of four subunits E1α, E1β, E2, and E3, is responsible for the breakdown the amino acids leucine, isoleucine, and valine, which exist in many protein-rich foods. The four subunits of the complex are coded by the genes BCKDHA, BCKDHB, DBT, and DLD. Each of these genes code for a single subunit, and any mutation occurring in both alleles encoding a subunit will result in the disorder (Podebrad et al 1999). No other phenotype has been known to be associated with these mutations. Although the most common mutation is found on the BCKDHA gene on the 19th chromosome, mutations on any of the four genes result in indistinguishable consequences (Strauss et al. 2013). In other words, a mutation on any one of the genes translates to a non-functional branched-chain alpha-ketoacid dehydrogenase complex that does not produce the necessary enzymes for normal breakdown of proteins.
Diagnosis and Symptoms.
There are a few, relatively easy ways to test for MSUD.