A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction.

Abstract

Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.

• Authors: Masamune Sakamoto, Den Kouhei, Muzhirah Haniffa, Sebastián Silva, Mónica Troncoso, Paola Santander, Valeria Schonstedt, Ximena Stecher, Nobuhiko Okamoto, Kohei Hamanaka, Takeshi Mizuguchi, Satomi Mitsuhashi, Noriko Miyake, Naomichi Matsumoto
• Journal: Journal of human genetics (J Hum Genet) Vol. 65 Issue 9 Pg. 751-757 (Sep 2020) ISSN: 1435-232X [Electronic] England
• PMID: 32405030 (Publication Type: Case Reports, Journal Article)

Chemical References

• Pyrophosphatases
• ITPA protein, human

Topics

• Brain Diseases (complications, enzymology, genetics, mortality)
• Corpus Callosum (diagnostic imaging, pathology)
• Developmental Disabilities (complications, enzymology, genetics, mortality)
• Epilepsy (complications, enzymology, genetics, mortality)
• Female
• Genetic Predisposition to Disease
• Genotype
• Homozygote
• Humans
• Infant
• Magnetic Resonance Imaging
• Male
• Multiple Organ Failure (complications, enzymology, genetics, mortality)
• Muscle Hypotonia (complications, enzymology, genetics, mortality)
• Mutation
• Pedigree
• Pyramidal Tracts (diagnostic imaging, pathology)
• Pyrophosphatases (genetics)
• Exome Sequencing