Abstract|Mixed Topics 2| Volume 357, SUPPLEMENT 1, e43-e44, October 15, 2015

Genetic profiling of Indian patients with glutaric acidemia type I

      Background: Glutaric acidemia type I (GA-I), is an inborn error of metabolism caused due to deficiency of the enzyme Glutaryl-CoA Dehydrogenase. There are very few studies on the genetic etiology of GA-I from India.
      Objective: The objective of this study was to screen Indian patients with GA-I for commonly occurring high and low excretor mutations.
      Materials and methods: The study was approved by the institutional Human Ethics Committee. Fifty confirmed GA-I patients from unrelated families were recruited based on clinical, neuroimaging and biochemical profiles. Informed consent was obtained from patients before taking blood spots on the filter paper and screened for mutations, R402W, A421V and A293T (high excretor) and R227P and V400M (low excretor) by RFLP or by direct sequencing of PCR products. Mutations screened by RFLP were further confirmed by sequencing.
      Results: Among the patients, 11(22%) were found to have R402W mutation, 7(14%) were homozygous and 5(8%) were heterozygous. One(2%) had F236L and 1(2%) had R313W mutations. Novel mutations, P286S was found in 2(4%), W225X in 1(2%), H403Y in 1(2%), Y295Y in 1(2%) and 1606 G > T at 3’ UTR in 1 (2%). Conversely, none of the GA-I patients had A421V, A293T, R227P and V400M mutations. No novel low excretor mutations were found.
      Conclusion: From this study, it is evident that R402W and novel P286S mutations were common among GA-I patients. A421V, A293T, R227P and V400M mutations were found to be absent. In conclusion, R402W and P286S are the most prevalent mutations among GA-I patients from India.