A moderate increase of branched-chain amino acid metabolites in urine may result from lactic acidosis, episodic ketosis, or deficiencies of the vitamins, thiamine or lipoic acid.
A significant increase of branched-chain amino acid metabolites is associated with the genetic disorders maple syrup urine disease (=MSUD) and pyruvate dehydrogenase deficiency.
MSUD:
MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The symptoms of MSUD often show in infancy and lead to severe brain damage if untreated. MSUD may also present later depending on the severity of the disease. If left untreated in older individuals, during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme, or erratic behaviour and moods, hallucinations, anorexia, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma. In maple syrup urine disease, the brain concentration of branched-chain keto acids can increase 10- to 20-fold. This leads to a depletion of glutamate and a consequent reduction in the concentration of brain glutamine, aspartate, alanine, and other amino acids. The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis.
Potential treatment options:
Patients with slight to moderate elevations may use dietary supplements containing thiamine to improve clinical symptoms.
3-Methyl-2-oxovaleric acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids.
Moderate increase may result from lactic acidosis, episodic ketosis, or thiamine/lipoic acid deficiency. Significant elevations are associated with genetic issues, MSUD, and pyruvate dehydrogenase deficiency.
- Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
- Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.
3-Methyl-2-oxovaleric (Males Age 13 and Over)
