Limb-Girdle Muscular Dystrophy

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Limb-Girdle Muscular Dystrophy

Limb-Girdle Muscular Dystrophy

History of the Patient's Problem

We present the case of a patient with LGMD 2B misdiagnosed as polymyositis to further illustrate these diagnostic challenges. Informed consent in writing was obtained from our patient.

A 58-year-old woman developed slowly progressive proximal weakness in the lower limbs, which started in her third decade of life and later progressed to the upper extremities. EMG revealed a myopathy with abundant spontaneous activity and a muscle biopsy from 1995 revealed endomysial and perivascular inflammation. Polymyositis was diagnosed and high-dose prednisone was started. The patient experienced no improvement despite treatment for several years. In 2001 she was started on azathioprine.

In 2004, she underwent a new neurological evaluation. Her neurological exam revealed normal mental status and cranial nerves evaluation, hypoactive reflexes, proximal weakness (grade 2 in the proximal lower extremities and 4 in the arms), normal sensory and cerebellar testing, waddling gait with pronounced lordosis, inability to stand up from a chair without support. Slight atrophy in the proximal legs was noted. A neuropsychological evaluation was unremarkable. Her family history was significant for several reasons. First, her parents were second-degree cousins. Second, she reported that among her six brothers and sisters, two of them had a disease that resembled her condition. There were no other similar cases in the family, except for the daughter of one of the brothers, who started to subjectively complain of gait difficulties. In a second evaluation, she brought one of her brothers who had similar disease pattern. A familial LGMD was suspected. EMG confirmed the presence of a myopathy with abundant spontaneous activity, also involving the proximal upper extremities. The serum aldolase and creatine kinase levels were markedly elevated (15.6U/L and 2234UI/L respectively). Azathioprine was discontinued and prednisone was slowly tapered off. A new muscle biopsy was performed. It revealed dystrophic features and perivascular inflammation (Figure). Immunohistochemistry, which included identification of dystrophin, merosin, calpain, calveolin, alpha, beta, gamma and delta sarcoglycans and dysferlin staining demonstrated absence of dysferlin in skeletal muscle (Figure).

The diagnosis of LGMD type 2B was made. Prednisone was completely stopped after being slowly tapered off. Evaluation of the other symptomatic brothers revealed similar conditions. The youngest was 45-year-old and had fatigue and progressive muscle weakness for 20 years. Motor examination revealed proximal weakness and slight atrophy in the legs. Serum aldolase and creatine kinase levels were 31.0U/L and 3990UI/L respectively. The oldest is 66 years old and reported muscular weakness in lower limbs since he was 50 years old. After five years he was aware of decreased strength in upper limbs. He became wheelchair-bound in the last 4 years.

What This Disease Is All About?

Limb-girdle muscular dystrophy (LGMD) type 2B is caused by mutations in the dysferlin gene, located at cromossome 2p13.l-p13.3. This protein is normally expressed at the skeletal muscle, but in affected patients it is reduced or absent'. Disferlinopathies usually manifest in late adolescence or early adulthood. The progression is usually slow and most of the patients lose their ability to walk ...
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