pediatrics
Branched Chain Amino Acid Metabolism Disorders
Maple syrup urine disease
This is a group of Autosomal Recessive disorders caused by deficiency of one or more subunits of a dehydrogenase active in the 2nd step of branched-chain amino acid catabolism. Although quite rare, incidence is significant (perhaps 1/200 births) in Mennonite populations. Clinical manifestations include body fluid odor that smells like maple syrup (particularly strong in cerumen) and overwhelming illness in the first days of life, beginning with vomiting and lethargy, and progressing to seizures, coma, and death if untreated. Patients with milder forms of the disease may manifest symptoms only during stress (eg, infection, surgery). Biochemical findings are profound ketonemia and acidemia. Diagnosis of maple syrup urine disease is by finding elevated plasma levels of branched-chain amino acids (particularly leucine) and confirmed by genetic testing. (Also see Initial testing .) Acutely, treatment of maple syrup urine disease with peritoneal dialysis or hemodialysis may be required, along with IV hydration and nutrition (including protein restriction and high-dosedextrose). Patients should be closely monitored for cerebral edema and acute pancreatitis. Long-term management is restriction of dietary branched-chain amino acids; however, small amounts are required for normal metabolic function. Thiamin is a cofactor for the decarboxylation, and some patients respond favorably to high-dose thiamin (up to 200 mg orally once a day). An emergency plan for how to manage acute illness, which may provoke a metabolic crisis, should be in place. Liver transplantation is curative. 