calpain and Respiratory-Insufficiency

We describe a 70 year-old independently ambulatory man with a 10-year history of progressive axial and limb-girdle weakness, hyperCKemia, and a 5-year history of dyspnea requiring nocturnal ventilatory support due to a known c.1309C>T (p.Arg437Cys) variant and a novel in-frame deletion of exons 17-19 in the calpain-3 encoding gene (CAPN3). Pulmonary function tests revealed neuromuscular respiratory weakness. Biceps femoris biopsy showed chronic myopathic changes, numerous lobulated fibers, and reduced calpain-3 immunoreactivity. Muscle immunoblot showed markedly reduced calpain-3 expression. Respiratory insufficiency is uncommon in autosomal recessive calpainopathy, and generally develops in the advanced stages of the disease when individuals become wheelchair-dependent. Our patient broadens the phenotypic spectrum of recessive calpainopathy to include early respiratory insufficiency and also further expands its molecular spectrum.

Topics: Aged; Biopsy; Calpain; Exons; Humans; Male; Muscle Proteins; Muscular Dystrophies, Limb-Girdle; Mutation; Respiratory Insufficiency

Little is known about the frequency of cardiopulmonary failure in limb-girdle muscular dystrophy type 2A (calpainopathy) patients, although some studies have reported severe cardiomyopathy or respiratory failure.. To clarify the frequency of cardiopulmonary dysfunction in this patient population, we retrospectively reviewed the respiratory and cardiac function of 43 patients with calpainopathy.. Nine of the 43 patients had forced vital capacity (FVC) < 80%, and 3 used noninvasive positive pressure ventilation. Mean FVC was significantly lower in patients who were nonambulant and had normal creatine kinase levels. Only 1 patient had a prolonged QRS complex duration. Echocardiography revealed that 1 patient had very mild left ventricular dysfunction.. These findings suggest that patients with calpainopathy may develop severe respiratory failure, but cardiac dysfunction is infrequent. Muscle Nerve 55: 465-469, 2017.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calpain; Cardiomyopathies; Child; Electrocardiography; Female; Humans; Male; Middle Aged; Muscle Proteins; Muscular Dystrophies, Limb-Girdle; Mutation; Respiratory Insufficiency; Retrospective Studies; Vital Capacity; Young Adult