{Reference Type}: Case Reports
{Title}: Case report of a rare purine synthesis disorder due to 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR) deficiency.
{Author}: Joy P;Madhuri V;Palocaren T;Das S;Susan Cleave Abraham S;Korula S;Koshy B;Jose J;Chandran M;Danda S;Joy P;Madhuri V;Palocaren T;Das S;Susan Cleave Abraham S;Korula S;Koshy B;Jose J;Chandran M;Danda S;Joy P;Madhuri V;Palocaren T;Das S;Susan Cleave Abraham S;Korula S;Koshy B;Jose J;Chandran M;Danda S;
{Journal}: Brain Dev
{Volume}: 44
{Issue}: 9
{Year}: Oct 2022
{Factor}: 2.272
{DOI}: 10.1016/j.braindev.2022.05.004
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>CONCLUSIONS: </B>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.