Rare diseases
The prevalence is approximately 1/150,000 to 1/200,000 births.
Maple syrup urine disease (MSUD) is a hereditary disorder of the metabolism of branched chain amino acids (i.e., leukine, isoleukine and valine), caused by a deficiency of the mitochondrial complex branched-chain a-ketoacid dehydrogenase (BCKD). This complex represents the second enzyme 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.
The genes encoding the different components of the BCKD complex, namely E1-alpha, E1-beta, E2 and E3 are BCKDHA, BCKDHB, DBT and DLD, respectively.
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. These episodes are often caused by an increase in the catabolism of endogenous proteins that can be induced by an intercurrent disease, by exercise, injury, surgery or fasting. Clinical manifestations include epigastric pain, vomiting, anorexia, muscle fatigue, cognitive impairment and ataxia. In such cases, cerebral edema can lead to premature death.
The diagnosis of maple syrup disease is based on a measurement of plasma concentrations of branched amino acids (i.e., leukine, isoleukine, and valine). The concomitant presence of alloisoleukine is a pathognomonic marker of the disease. This parameter can be highlighted by an analysis of the plasma amino acid profile.
The disease is further confirmed by urinary organic acid analysis, which reveals the accumulation of branched ketoacids, as well as molecular analysis of the implicated genes.
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 mainstay of care is dietary restriction of connected amino acids. The response to thiamine (vitamin B1) treatment should be assessed.
The episodes of metabolic decompensation are managed by intravenous infusions of glucose. In rare circumstances, hemodialysis or peritoneal dialysis is necessary to eliminate connected amino acids and toxic ketoacids.
Maple syrup urine disease is inherited in an autosomal recessive manner.
NEONATAL MSUD Screening Assay is a quantitative enzymatic test that assays leukine, one of the 3 amino acids accumulated in maple syrup urine disease (MSUD) also known as ketoacidemia or branched-chain amino acids (BCAAs). This test is for maple syrup urine disease newborn screening, and is performed using dried blood samples on 903® or 226 type blotting paper.