Preferred Label : 3-hydroxyisobutyric aciduria;
Type : Phenotype or locus, molecular basis unknown;
Description : 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. *FIELD* RF 1. 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. 2. 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. 3. Sasaki, M.; Kimura, M.; Sugai, K.; Hashimoto, T.; Yamaguchi,
S. : 3-Hydroxyisobutyric aciduria in two brothers. Pediat. Neurol. 18: 253-255, 1998.
*FIELD* CS Metabolic: Organic acidemia; Episodic ketoacidosis; Lacticacidemia Growth:
Failure to thrive;
Inheritance : Autosomal recessive;
Prefixed ID : %236795;
Origin ID : 236795;
UMLS CUI : C0342737;
Currated CISMeF NLP mapping
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
