Congenital Megaconial Myopathy Due to a Novel Defect in the Choline Kinase beta (CHKB) Gene (P01.116)

Abstract

Objective: To describe the first American patient with mutations in the gene encoding choline kinase beta ( CHKB ), a novel cause of congenital muscular dystrophy with giant and displaced muscle mitochondria. Background Mutations in CHKB have been described in 15 children with congenital muscular dystrophy and mental retardation. The morphologic hallmark was the presence in muscle of giant mitochondria (megaconial myopathy) displaced to the periphery of the fibers (Mitsuhashi et al, 2011). Design/Methods: Here we describe a 2-year-old African American boy with weakness and psychomotor delay. At 22 months, he was not able to sit up and did not utter any intelligible word. He was severely hypotonic and had multiple dysmorphic features. Serum CK was elevated but lactate was normal. EMG showed a myopathic pattern and brain MRI revealed diffuse atrophy. Results: Both histochemistry and electron microscopy of a muscle biopsy showed greatly enlarged mitochondria, which were pushed to the periphery of the fibers. Biochemical analysis revealed severely decreased cytochrome c oxidase activity (30% of normal). The patient harbored a novel homozygous CHKB mutation (E392X). Conclusions: Besides confirming the phenotype of CHKB mutations, we propose that this disorder affects the MAM (mitochondria-associated-membrane) and the impaired phospholipid metabolism in MAM causes both the abnormal size and the displacement of muscle mitochondria. Supported by: NIH Grant HD32062 and by the Marriott Mitochondrial Disorders Clinical Research Fund (MMDCRF). EAS is supported by the Ellison Foundation. Disclosure: Dr. Gutierrez Rios has nothing to disclose. Dr. Kalra has nothing to disclose. Dr. Wilson has nothing to disclose. Dr. Tanji has nothing to disclose. Dr. Akman has nothing to disclose. Dr. Area has nothing to disclose. Dr. Schon has received personal compensation for activities with Athena Diagnostics. Dr. Schon has received license fee payments from Affymetrix. Dr. DiMauro has nothing to disclose.