P.15.10 Megaconial myopathy presenting as a progressive limb-girdle myopathy

Megaconial myopathies are known as rare and severe autosomal recessive, early-onset pediatric diseases caused by mutations in the CHKB gene, characterized on muscle biopsy by the presence of giant mitochondria. We present here a 50-year old male, stemming from a Jewish consanguineous Lebanese family, who developed progressive muscle wasting and weakness form age 5 years on. The course was slowly progressive; the patient remained ambulant until age 37 years. He displayed episodes of regressive paroxysmal supraventricular tachyarrhythmia at age 46 and 47 years, and a severe restrictive respiratory insufficiency from his early thirties. The patient underwent three muscle biopsies, at age 28, 39 and 49 years. Diagnosis was suspected on the last biopsy, showing an uneven distribution of the intermyofibrillary network associating peripheral giant mitochondria with central areas devoid of organelles. Electron microscopy confirmed the presence of numerous giant mitochondria spanning up to two or more sarcomeres and reaching 1.2–1.8 μm in length and 0.6–0.8 μm in width. Retrospective analysis of the two first biopsies found some similar abnormalities. The patient harbours a homozygous c.499A > T (p.Ile167Phe) substitution in exon 4 of the mutation of the CHKB gene. A whole-body MRI was performed at the age of 42. A diffuse and severe fatty replacement (Mercuri 4) of muscles was detectable. Masticatory muscles and tongue as well as forearms, rectus femoris at thighs and anterior compartment of the legs were totally or partially preserved. This case, resembling a congenital myopathy, differs from the usual pattern of megaconial myopathies and expands the clinical spectrum of this disorder.