Epileptic apnea in a patient with inherited glycosylphosphatidylinositol anchor deficiency and PIGT mutations

Kosuke Kohashi, Akihiko Ishiyama*, Shota Yuasa, Tomomi Tanaka, Kazushi Miya, Yuichi Adachi, Noriko Sato, Hirotomo Saitsu, Chihiro Ohba, Naomichi Matsumoto, Yoshiko Murakami, Taroh Kinoshita, Kenji Sugai, Masayuki Sasaki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (SciVal)

Abstract

We report an 11-month-old boy with acetazolamide-responsive epileptic apnea and inherited glycosylphosphatidylinositol (GPI)-anchor deficiency who presented with decreased serum alkaline phosphatase associated with compound PIGT mutations. The patient exhibited congenital anomalies, severe intellectual disability, and seizures, including epileptic apnea with epileptiform discharges from bilateral temporal areas. Brain magnetic resonance imaging revealed delayed myelination and progressive atrophy of the brainstem, cerebellum, and cerebrum. Whole-exome sequencing revealed compound heterozygous mutations in PIGT (c.250 G > T, p.Glu84X and c.1096 G > T, p.Gly366Trp), which encodes a subunit of the GPI transamidase complex. Flow cytometry revealed decreased expression of CD16 (a GPI anchor protein) on granulocytes, supporting the putative pathogenicity of the mutations. Phenobarbital, clonazepam, and potassium bromide decreased the frequency of tonic seizure and acetazolamide decreased epileptic apnea. To our knowledge, this is the first reported case of intractable seizures accompanied by epileptic apnea associated with GPI anchor deficiency and a compound PIGT mutation.

Original languageEnglish
Pages (from-to)53-57
Number of pages5
JournalBrain and Development
Volume40
Issue number1
DOIs
StatePublished - 2018/01

Keywords

  • Epileptic apnea
  • Gamma-aminobutyric acid
  • Glycosylphosphatidylinositol anchor deficiency
  • Multiple congenital anomalies-hypotonia-seizures syndrome-3

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

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