Article: article from journal or magazin.
Case report (case report): feedback on an observation with a short commentary.
Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria.
Molecular Genetics and Metabolism
Publication types: Case Reports ; Journal ArticlePublication Status: ppublish
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.
Alcohol Oxidoreductases/genetics, Alcohol Oxidoreductases/metabolism, Cells, Cultured, Child, Preschool, DNA/genetics, DNA Mutational Analysis, Genome, Human/genetics, Humans, Hydroxybutyrates/chemistry, Hydroxybutyrates/metabolism, Male, Metabolism, Inborn Errors/enzymology, Metabolism, Inborn Errors/genetics, Recombinant Fusion Proteins/metabolism, Valine/metabolism
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