Clinical Information

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. The BCKDH complex is involved in the metabolism of the branched-chain amino acids (BCAA): isoleucine, leucine, and valine. MSUD can be divided into 5 phenotypes: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase (E3)-deficient, depending on the clinical presentation and response to thiamin administration. Classic MSUD, the most common and most severe form, presents in the neonate with feeding intolerance, failure to thrive, vomiting, lethargy, and maple syrup odor to urine and cerumen. If untreated, it progresses to irreversible intellectual disabilities, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.

Age of onset for individuals with variant forms of MSUD is variable and some have initial symptoms as early as 2 years of age. Symptoms include poor growth and feeding, irritability, and developmental delays. These patients can also experience severe metabolic intoxication and encephalopathy during periods of sufficient catabolic stress.

MSUD is a panethnic condition but is particularly prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania with an incidence of 1:760 live births. The incidence of MSUD is approximately 1:185,000 live births in the general population.

Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids. Because BCAA are essential amino acids, the dietary treatment requires frequent adjustment, which is accomplished by regular determination of BCAA and allo-isoleucine concentrations. Orthotopic liver transplantation has been used with success and is an effective therapy for MSUD.