A Cardiomyopathy in a Patient With Limb Girdle Muscular Dystrophy Type 2A

Abstract

L imb girdle muscular dystrophy (LGMD) is a muscular dystrophy with predominantly proximal distribution of weakness that spares the distal, facial, and extraocular muscles early in the course of the disease. Cardiac muscle may be affected, which may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias. Significant cardiac involvement has been documented frequently in LGMD2C-F, 2I, and LGMD1B forms of the disease, rarely in the LGMD1C and 2B subtypes, and thus far have not been reported in type 2A. We report a presentation of severe cardiomyopathy in an adult with muscular dystrophy type 2A.A 23-year-old black man was seen in hospital with complaints of decreased exercise tolerance, dyspnea on exertion, orthopnea, and some presycopal episodes for several weeks.The patient's LGMD was diagnosed at the age of 21 years. No family history of similar problems was noted. Physical examination at the time revealed decreased strength in the shoulder girdle area, with inability to raise the arm over the head. Laboratory data at the time showed a creatinine kinase of 4263 U/L and serum troponin of 0.77 ng/mL. ECG revealed sinus rhythm with bifascicular block. The patient's blood was then sent for genetic testing, which demonstrated CAPN3 sequencing alteration (Athena Diagnostics, Inc).When seen by cardiology, he was noted to be alert and oriented, afebrile, and normotensive. On physical examination he was noted to have jugular venous distension, with cardiac examination significant for a grade III/VI holosystolic murmur at the left lower sternal border, with a displaced point of maximal impulse. ECG revealed normal sinus rhythm, right bundle-branch block, and left anterior fascicular block. Laboratory tests revealed a BNP of 541 pg/mL, with negative cardiac enzymes. His other laboratory tests were found to be within normal limits. An echocardiogram was notable for severely reduced right and left ventricular systolic function, left ventricular ejection fraction of 15%, severe tricuspid regurgitation, and findings suggestive of left ventricular noncompaction (Figure). The patient was treated with ACE inhibitors, β blockers, and diuretics, with no improvement in his cardiac function on subsequent echocardiography. He had few evidence to suggest possible secondary causes of his cardiomyopathy, including myocarditis and ischemic disease, although he refused more extensive testing. DiscussionSignificant cardiac involvement has been rarely documented in LGMD1C, 2A, and 2B, whereas it is relatively common in LGMD2C, 2D, 2E, 2F, 2I, and LGMD1B. This may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias.LGMD1B patients often exhibit findings of both cardiomyopathy and dysrhythmia. 1LGMD2A (calpainopathy) is found as a result of a mutation of chromosome 15 in the CAPN3 gene encoding the proteolytic enzyme calpain-3.2 Calpain-3 (p94) belongs to the calpain family of soluble intracellular cysteine proteases, the majority of which are activated by a calcium-dependent mechanism. Calpain-3 is not, ...

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