Maple Syrup Urine Disease (MSUD)

In the first reaction of the NEONATAL MSUD Screening Assay, an enzyme, the leucine dehydrogenase, converts BCAAs in the sample to α-ketoisocaproate acid and NADH. Thereafter, the presence of NADH is quantified by colorimetry using tetrazolium salt. The results are read by measuring absorbance for which staining intensity will be proportional to the concentration of BCAAs in the sample.

Maple syrup urine disease (MSUD) is a hereditary disorder of the metabolism of branched chain amino acids (leucine, isoleucine and valine), caused by a deficiency of the mitochondrial complex branched-chain a-ketoacid dehydrogenase (BCKD). This complex is essential in the catabolic pathway of the three amino acids in question. MSUD is therefore characterized by an accumulation of connected amino acids as well as their catabolic intermediates, branched keto acids.

Several forms of maple syrup urine disease are described: the classic neonatal form in babies, marked by severe neurological toxicity, the subacute form with later detection, the intermittent form and the thiamine-sensitive form.

Maple syrup urine disease symptoms in newborns are clinically characterized by psychomotor retardation, eating disorders and a characteristic odor of maple syrup in urine. If left untreated, encephalopathy and central respiratory failure develop rapidly, coma occurs seven to ten days after birth. Episodes of metabolic intoxication may then occur in older children who are usually under nutritional control. The two main approaches in how to treat maple syrup urine disease include long-term daily dietary management, and treatment of acute metabolic decompensation episodes.

The diagnosis of maple syrup disease is based on a measurement of plasma concentrations of branched amino acids (leukine, isoleukine, and valine).