TY - JOUR
T1 - Ketogenic diet for refractory epilepsy with MEHMO syndrome
T2 - Caution for acute necrotizing pancreatitis
AU - Mori, Mioko
AU - Kumada, Tomohiro
AU - Inoue, Kenji
AU - Nozaki, Fumihito
AU - Matsui, Katsuyuki
AU - Maruo, Yoshihiro
AU - Yamada, Mamiko
AU - Suzuki, Hisato
AU - Kosaki, Kenjiro
AU - Shibata, Minoru
N1 - Publisher Copyright:
© 2021 The Japanese Society of Child Neurology
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Acute necrotizing pancreatitis
KW - Epileptic seizures
KW - Hypogonadism and hypogenitalism
KW - Intellectual disability
KW - Ketogenic diet therapy
KW - MEHMO
KW - Microcephaly, and obesity syndrome
KW - Refractory epilepsy
KW - γ-subunit of eukaryotic translation initiation factor 2 (eIF2)
UR - http://www.scopus.com/inward/record.url?scp=85103370833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103370833&partnerID=8YFLogxK
U2 - 10.1016/j.braindev.2021.02.002
DO - 10.1016/j.braindev.2021.02.002
M3 - Article
C2 - 33714664
AN - SCOPUS:85103370833
VL - 43
SP - 724
EP - 728
JO - Brain and Development
JF - Brain and Development
SN - 0387-7604
IS - 6
ER -