Identification of a novel homozygous variant confirms ITPA as a developmental and epileptic encephalopathy gene

Am J Med Genet A. 2019 May;179(5):857-861. doi: 10.1002/ajmg.a.61103. Epub 2019 Feb 28.


ITPA related epileptic encephalopathy (epileptic encephalopathy, early infantile, 35) is a rare inborn error of metabolism. All reported individuals with this condition, including the present case manifest global developmental delay, seizures, progressive postnatal microcephaly, hypotonia, thin corpus callosum, cerebral atrophy, delayed myelination and white matter changes in posterior limb of internal capsule. Cataract and dilated cardiomyopathy are other characteristic findings. Currently, a single publication describes this condition in four families. Three truncating and two missense variants in ITPA have been identified in these families. We hereby report another family with ITPA related disorder and review the genotype and phenotype of the reported subjects.

Keywords: ITPA; ITPase; epileptic encephalopathy; hypomyelination; purine metabolism disorders.

Publication types

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

MeSH terms

  • Alleles
  • Brain / abnormalities
  • Brain / diagnostic imaging
  • Consanguinity
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics*
  • Female
  • Genotype
  • Homozygote*
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Protein Conformation
  • Pyrophosphatases / chemistry
  • Pyrophosphatases / genetics*
  • Spasms, Infantile / diagnosis*
  • Spasms, Infantile / genetics*


  • Pyrophosphatases
  • ITPA protein, human