Neonatal symptoms are non-specific and include poor feeding, vomiting, progressing to decreased level of consciousness. An odor of sweaty feet is be best appreciated in body sweat or (in older patients) cerumen from the ear. Acidosis with an unexplained anion gap is characteristic, and hyperammonemia, hyper- or hypoglycemia and hypocalcemia can be present. Pancytopenia as well as isolated neutropenia and thrombocytopenia can occur due to bone marrow suppression. Left untreated, patients can progress to coma and death often due to cerebral edema or hemorrhage. Later episodes resemble neonatal ones, though are usually less severe. Adult onset disease has rarely been reported in patients with severe stress, such as excessive exercise. Characteristic metabolites include C5-carnitine identified by tandem mass spectrometry and isovaleric acid and/or isovalerylglycine in urine organic acids. Glycine levels are typically elevated in blood. Newborn screening by tandem mass spectrometry can identify affected newborns prior to onset of symptoms, but also identifies a cohort of babies with a common variant c.932C>T (p.A282V) that causes biochemical findings, but not disease.
IVD