Next generation sequencing elucidated a clinically undiagnosed metabolic disorder - An Iranian family with hereditary orotic aciduria

Abstract Hereditary orotic aciduria is a rare autosomal recessive metabolic disorder, manifested by retarded growth, developmental delay and elevated levels of orotic acid in the urine. It is the result of defect in the UMPS gene causing a glitch in the pyrimidine synthesis pathway. Orotic aciduria has a broad range of mimicking disorders including diverse metabolic and mitochondrial conditions. Precise diagnosis of the disease is time saving and key to efficient treatment. Based on the patient's clinical diagnosis, age of onset and family history, Whole Exome Sequencing (WES) technique was applied to determine the causative variant. One novel missense mutation was identified in the UMPS gene. Family screening verified heterozygosity of the variant in the parents. This study positively contributes to rapid detection and timely diagnosis of orotic aciduria in Iranian patients. It may also enrich the mutation spectrum of the UMPS gene worldwide.