SNOMEDCT: 237957007; ORPHA: 939;
Ko et al. (1991) described a 6-year-old Caucasian boy with a clinical picture typical of organic acidemia with repeated episodes of ketoacidosis. He showed marked failure to thrive and chronic lactic acidemia. Urinary excretion of 3-hydroxyisobutyric acid ranged from 170 to 390 mmol/mol of creatinine. Administration of valine increased the excretion strikingly and reproduced the clinical picture of ketoacidosis. Concentrations of free carnitine were low and esterified carnitine was elevated. Treatment with carnitine and a diet restricted in protein appeared to be beneficial. This is a disorder of valine metabolism; see also methacrylic aciduria (250620). Ko et al. (1991) speculated that the fundamental defect was in 3-hydroxyisobutyrate dehydrogenase, which catalyzes the conversion of 3-hydroxyisobutyrate to methylmalonic semialdehyde, or in the conversion of the semialdehyde to propionyl CoA. They favored the latter possibility.
Chitayat et al. (1992) reported the association of 3-hydroxyisobutyric aciduria with brain dysgenesis. They described monozygotic male twins, born to nonconsanguineous parents, who had dysmorphic facial features, microcephaly, migrational brain disorder, and congenital intracerebral calcification. In addition to excreting excessive amounts of 3-hydroxyisobutyric acid, they had evidence of impaired oxidative metabolism and metabolic acidosis. The level of 3-hydroxyisobutyrate in stored samples of midtrimester amniotic fluid was found to be high. Thus, this disorder is potentially amenable to prenatal diagnosis.
Sasaki et al. (1998) described 2 Japanese brothers with 3-hydroxyisobutyric aciduria. The elder brother died in a ketoacidotic episode at the age of 4 years; the younger brother also manifested repeated episodes of ketoacidosis after 1 year of age. The diagnosis of 3-hydroxyisobutyric aciduria was made by gas chromatography/mass spectrometry analysis, using the unique fragment ions of 3-hydroxyisobutyric acid. Magnetic resonance imaging revealed focal white matter abnormalities. Protein restriction was effective in preventing ketoacidotic episodes, although carnitine therapy was seen as less effective.
Chitayat, D., Meagher-Villemure, K., Mamer, O. A., O'Gorman, A., Hoar, D. I., Silver, K., Scriver, C. R. Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria. J. Pediat. 121: 86-89, 1992. [PubMed: 1625099] [Full Text: https://doi.org/10.1016/s0022-3476(05)82549-1]
Ko, F.-J., Nyhan, W. L., Wolff, J., Barshop, B., Sweetman, L. 3-Hydroxyisobutyric aciduria: an inborn error of valine metabolism. Pediat. Res. 30: 322-326, 1991. [PubMed: 1956714] [Full Text: https://doi.org/10.1203/00006450-199110000-00006]
Sasaki, M., Kimura, M., Sugai, K., Hashimoto, T., Yamaguchi, S. 3-Hydroxyisobutyric aciduria in two brothers. Pediat. Neurol. 18: 253-255, 1998. [PubMed: 9568924] [Full Text: https://doi.org/10.1016/s0887-8994(97)00161-6]