TY - JOUR
T1 - Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria
AU - Loupatty, Ference J.
AU - van der Steen, Annemarie
AU - Ijlst, Lodewijk
AU - Ruiter, Jos P. N.
AU - Ofman, Rob
AU - Baumgartner, Matthias R.
AU - Ballhausen, Diana
AU - Yamaguchi, Seiji
AU - Duran, Marinus
AU - Wanders, Ronald J. A.
PY - 2006
Y1 - 2006
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.ymgme.2005.09.019
DO - https://doi.org/10.1016/j.ymgme.2005.09.019
M3 - Article
C2 - 16466957
SN - 1096-7192
VL - 87
SP - 243
EP - 248
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 3
ER -