Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis

Mioko Mori, Tomohiro Kumada, Kenji Inoue, Fumihito Nozaki, Katsuyuki Matsui, Yoshihiro Maruo, Mamiko Yamada, Hisato Suzuki, Kenjiro Kosaki, Minoru Shibata

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients’ quality of life. Case: A 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient's clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient's refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death. Conclusion: The pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.

Original languageEnglish
Pages (from-to)724-728
Number of pages5
JournalBrain and Development
Volume43
Issue number6
DOIs
Publication statusPublished - 2021 Jun

Keywords

  • Acute necrotizing pancreatitis
  • Epileptic seizures
  • Hypogonadism and hypogenitalism
  • Intellectual disability
  • Ketogenic diet therapy
  • MEHMO
  • Microcephaly, and obesity syndrome
  • Refractory epilepsy
  • γ-subunit of eukaryotic translation initiation factor 2 (eIF2)

ASJC Scopus subject areas

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

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