The neurotoxicity is apparently due to excess phenylalanine, and NOT lack of tyrosine. However, the mechanism of neurotoxicity is unknown. Lack of BH 4 can be caused by mutations in several genes, including the reductase and enzymes involved in its synthesis. Untreated, MSUD causes abnormal brain development, mental retardation and death within a few months. Patients must be treated within ten days of birth to achieve normal intellect.
Treatment is the dietary restriction of branched chain amino acids.
In the most severe form, MSUD causes severe acidosis during the first week of life. This is characterized by progressively poorer feeding, vomiting , seizures , lethargy , and finally coma . Untreated infants die in the first few weeks of life. MSUD also occurs in an intermittent form and a mild form. Even the mildest form, MSUD results in retardation and bouts of acidosis precipitated by stresses such as illness.