Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria.
Article Details
- CitationCopy to clipboard
Loupatty FJ, van der Steen A, Ijlst L, Ruiter JP, Ofman R, Baumgartner MR, Ballhausen D, Yamaguchi S, Duran M, Wanders RJ
Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria.
Mol Genet Metab. 2006 Mar;87(3):243-8. Epub 2006 Feb 8.
- PubMed ID
- 16466957 [ View in PubMed]
- Abstract
3-Hydroxyisobutyric aciduria is a rare entity and affected individuals display a range of clinical manifestations including dysmorphic features and neurodevelopmental problems in the majority of patients. Here, we present two novel patients with 3-hydroxyisobutyric aciduria. To our knowledge, these are the 11th and 12th cases of 3-hydroxyisobutyic aciduria reported. It is believed that a deficiency in 3-hydroxyisobutyrate dehydrogenase is the most likely cause of this disorder. Measurement of 3-hydroxyisobutyrate dehydrogenase activity in fibroblasts homogenates of the two newly identified patients and a previously reported patient, however, revealed similar activities as in control fibroblasts. Since other enzymes with overlapping substrate specificity could conceal abnormal 3-hydroxyisobutyrate dehydrogenase activity, we cloned a candidate human cDNA for 3-hydroxyisobutyrate dehydrogenase (HIBADH). By heterologous expression in Escherichia coli, we showed that the product of the HIBADH gene indeed displays 3-hydroxyisobutyrate dehydrogenase activity. Mutation analysis of the corresponding gene in the patients suffering from 3-hydroxyisobutyric aciduria revealed no mutations. We conclude that HIBADH is not the causative gene in 3-hydroxyisobutyric aciduria.