P.5.15 Diagnostic challenge and therapeutic dilemma in necrotizing myopathy

Abstract

LGMD2L is caused by mutations in the anoctamin-5-gene (ANO5). Limb-girdle muscle weakness can also be caused by an immune-mediated necrotizing myopathy (IMNM) with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase (HMGCR), which catalyzes a rate-limiting step in cholesterol biosynthesis and is inhibited by statins. We report on a 44-year-old patient with LGMD2L and HMGCR-associated-IMNM without previous statin exposure. He presented with myalgia, dysphagia and slowly progressive proximal weakness in the legs for four years. CK-levels were permanently increased (5000–7500 U/l). HMGCR-antibodies were detected in serum (D-Tek, Mons, Belgium). Electromyography and cardiac exams were normal. Vital capacity was mildly reduced (70%). Muscle biopsy revealed necrotic fibers and basophilic regenerating muscle fibers, without inflammation. Several fibers showed an abnormal MHC-I staining at their membranes. The MAC stain was normal. A whole-body muscle-MRI revealed symmetrical fatty degeneration in hamstrings and medial gastrocnemius muscles, without inflammatory changes. Based on this characteristic MRI pattern, which is unusual for IMNM and has been reported in LGMD2L, direct sequencing of ANO5 was performed and two known pathogenic compound heterozygous mutations were identified. Because of the presence of HMGCR-autoantibodies, oral steroids were started. Six weeks later, the patient suffered no longer from myalgia, the Mingazzini maneuver ameliorated, a swallowing test improved, CK-levels significantly decreased (from 5098 to 1900 U/l) and HMGCR-antibodies were no longer detectable. We conclude that it might be useful to screen for additional hereditary causes of necrotizing myopathies in statin-unexposed HMGCR-IMNM patients. Besides the diagnostic challenge, our case indicates the therapeutic dilemma of immunosuppressive treatment regimen in “double trouble necrotizing myopathies” which might be more frequent than previously suspected.