Case report of a rare purine synthesis disorder due to 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR) deficiency

Background AICA (5-aminoimidazole-4-carboxamide) ribosiduria is an inborn error in purine biosynthesis caused due to biallelic pathogenic variants in the 5-aminoimidazole-4-carboxamide ribonucleotide-formyltransferase/imp cyclohydrolase (ATIC) gene located on chromosome 2q35. ATIC codes for a bifunctional enzyme, AICAR transformylase and inosine monophosphate (IMP) cyclohydrolase, which catalyse the last two steps of de novo purine synthesis. This disorder has been previously reported in only 4 cases worldwide, and herein, we report the first from India. Case Report The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant. Conclusion This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling.