Identification of a New IVD Gene Mutation in a Patient with Isovaleric Acidemia

Abstract

Introduction: Isovaleric acidemia is the first recognized organic acidemia disorder in humans caused by a defect in the enzyme isovaleryl-coenzyme A dehydrogenase. There are some cases of this disease in the northern provinces of Iran, where there is a high rate of consanguineous marriages. Therefore, this study aims to identify mutations occurring in patients with isovaleric acidemia diagnosed.

Methods: The patient is a 5-year-old male child (weight: 21 kg, height: 105.5 cm, blood group AB+) with a learning and speech disorder. Routine blood and urine tests, as well as metabolic abnormalities tests such as amino acid abnormalities and fatty acid oxidation, were performed. The DNA was extracted from the blood samples of the patient and nine family members and sequenced using the Sanger method.

Results: The carnitine/acylcarnitine profile showed an increased amount of isovalerylcarnitine (C5=4.74 micromol/l, cutoff>0.47 micromol/l). Furthermore, in the urine organic acids test, an increase in isovalerylglycine (91.02%, cutoff<0.69) was observed. A new mutation, c.391A>T, was identified in exon 4 of the IVD gene. Some members of the patient's family were also heterozygous.

Conclusion: The results indicated that the patient has a new mutation (c.391A>T) in the IVD gene, which leads to a change of amino acid asparagine to tyrosine.