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MED23 ‐associated refractory epilepsy successfully treated with the ketogenic diet
Author(s) -
Lionel Anath C.,
Monfared Nasim,
Scherer Stephen W.,
Marshall Christian R.,
MercimekMahmutoglu Saadet
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37802
Subject(s) - ketogenic diet , epilepsy , microcephaly , global developmental delay , exome sequencing , medicine , hypotonia , galactosemia , corpus callosum , phenotype , pediatrics , refractory (planetary science) , endocrinology , biology , genetics , pathology , galactose , psychiatry , biochemistry , astrobiology , gene
We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5‐year‐old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23 . MED23 is a regulator of energy homeostasis and glucose production. Liver‐specific Med23‐knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc.