Branched-chain keto acid decarboxylation is defective in
Maple syrup urine disease Maple syrup urine disease (MSUD) is a rare (1:185,000), autosomal recessive disorder in which there is a paial or complete deficiency in BCKD, a mitochondrial enzyme complex that oxidatively decarboxylates leucine, isoleucine, and valine (see Figure 20.10). These BCAAs and their corresponding a-keto acids accumulate in the blood, causing a toxic effect that interferes with brain functions. The disease is characterized by feeding problems, vomiting, ketoacidosis, changes in muscle tone, neurologic problems that can result in coma (primarily due to the rise in leucine), and a characteristic maple syrup-like odor of the urine due to the rise in isoleucine. If untreated, the disease is fatal. If treatment is delayed, intellectual disability results. 1. Classification: The term "maple syrup urine disease" includes a classic type and several variant forms of the disorder. The classic, neonatal-onset form is the most common type of MSUD. Leukocytes or cultured skin fibroblasts from these patients show little or no BCKD activity. Infants with classic MSUD show symptoms within the first several days of life. If not diagnosed and treated, classic MSUD is lethal in the first weeks of life. Patients with intermediate forms have a higher level of enzyme activity (up to 30% of normal). The symptoms are milder and show an onset from infancy to adolescence. Patients with the rare thiamine-dependent variant of MSUD respond to large doses of this vitamin. 2. Screening and diagnosis: As with PKU, prenatal diagnosis and neonatal screening are available, and most affected individuals are compound heterozygotes. 3. Treatment: MSUD is treated with a synthetic formula that is free of BCAAs, supplemented with limited amounts of leucine, isoleucine, and valine to allow for normal growth and development without producing toxic levels. Early diagnosis and lifelong dietary treatment is essential if the child with MSUD is to develop normally.
Alkaptonuria
GM1 gangliosidosis
Maple syrup urine disease
Hanup's disease
Metabolism of protein and amino acid