Case Report| Volume 44, ISSUE 9, P645-649, October 2022

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



      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.


      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.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Baresova V.
        • Skopova V.
        • Sikora J.
        • Patterson D.
        • Sovova J.
        • Zikanova M.
        • et al.
        Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency.
        Hum Mol Genet. 2012; 21: 1534-1543
        • Ramond F.
        • Rio M.
        • Héron B.
        • Imbard A.
        • Marie S.
        • Billiemaz K.
        • et al.
        AICA-ribosiduria due to ATIC deficiency: Delineation of the phenotype with three novel cases, and long-term update on the first case.
        J Inherit Metab Dis. 2020; 43: 1254-1264
        • Marie S.
        • Heron B.
        • Bitoun P.
        • Timmerman T.
        • Van den Berghe G.
        • Vincent M.-F.
        AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC.
        Am J Hum Genet. 2004; 74: 1276-1281
      1. Squires J. Bricker D. Twombly E. Ages & stages questionnaires: social-emotional, 2nd ed: A parent-completed child monitoring system for social-emotional behaviors. Paul H. Brookes Publishing Co Inc, Baltimore2015
        • Fadista J.
        • Oskolkov N.
        • Hansson O.
        • Groop L.
        LoFtool: a gene intolerance score based on loss-of-function variants in 60 706 individuals.
        Bioinformatics. 2017; 33: 471-474
        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • et al.
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
        Genet Med. 2015; 17: 405-424
        • Greasley S.E.
        • Horton P.
        • Ramcharan J.
        • Beardsley G.P.
        • Benkovic S.J.
        • Wilson I.A.
        Crystal structure of abifunctionaltransformylase and cyclohydrolase enzyme in purine biosynthesis.
        Nat Struct Biol. 2001; 8: 402-406
        • Laikind P.K.
        • Seegmiller J.E.
        • Gruber H.E.
        Detection of 5'-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton-Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity.
        Anal Biochem. 1986; 156: 81-90