AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC

Am J Hum Genet. 2004 Jun;74(6):1276-81. doi: 10.1086/421475. Epub 2004 Apr 26.


In a female infant with dysmorphic features, severe neurological defects, and congenital blindness, a positive urinary Bratton-Marshall test led to identification of a massive excretion of 5-amino-4-imidazolecarboxamide (AICA)-riboside, the dephosphorylated counterpart of AICAR (also termed "ZMP"), an intermediate of de novo purine biosynthesis. ZMP and its di- and triphosphate accumulated in the patient's erythrocytes. Incubation of her fibroblasts with AICA-riboside led to accumulation of AICAR, not observed in control cells, suggesting impairment of the final steps of purine biosynthesis, catalyzed by the bifunctional enzyme AICAR transformylase/IMP cyclohydrolase (ATIC). AICAR transformylase was profoundly deficient, whereas the IMP cyclohydrolase level was 40% of normal. Sequencing of ATIC showed a K426R change in the transformylase region in one allele and a frameshift in the other. Recombinant protein carrying mutation K426R completely lacks AICAR transformylase activity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / metabolism*
  • Blindness / congenital
  • Child, Preschool
  • Erythrocytes / metabolism
  • Female
  • Fibroblasts / drug effects
  • Humans
  • Hydroxymethyl and Formyl Transferases / deficiency
  • Hydroxymethyl and Formyl Transferases / genetics*
  • Metabolism, Inborn Errors / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Nucleotide Deaminases / genetics*
  • Nucleotide Deaminases / metabolism
  • Phosphoribosylaminoimidazolecarboxamide Formyltransferase
  • Purines / biosynthesis*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Ribonucleotides / metabolism*


  • Purines
  • Recombinant Proteins
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Hydroxymethyl and Formyl Transferases
  • Phosphoribosylaminoimidazolecarboxamide Formyltransferase
  • Nucleotide Deaminases
  • IMP cyclohydrolase
  • AICA ribonucleotide

Associated data

  • GENBANK/BC008879
  • RefSeq/NT_005403