Clinical and pathological characteristics of four Korean patients with limb-girdle muscular dystrophy type 2B

Abstract

Limb-girdle muscular dystrophy type 2B (LGMD2B), a subtype of autosomal recessive limb-girdle muscular dystrophy (ARLGMD), is characterized by a relatively late onset and slow progressive course. LGMD2B is known to be caused by the loss of the dysferlin protein at sarcolemma in muscle fibers. In this study, the clinical and pathological characteristics of Korean LGMD2B patients were investigated. Seventeen patients with ARLGMD underwent muscle biopsy and the histochemical examination was performed. For the immunocytochemistry, a set of antibodies against dystrophin, alpha, beta, gamma, delta-sarcoglycans, dysferlin, caveolin-3, and beta-dystroglycan was used. Four patients (24%) showed selective loss of immunoreactivity against dysferlin at the sarcolemma on the muscle specimens. Therefore, they were classified into the LGMD2B category. The age at the onset of disease ranged from 9 yr to 33 yr, and none of the patients was wheelchair bound at the neurological examination. The serum creatine kinase (CK) was high in all the patients (4010-5310 IU/L). The pathologic examination showed mild to moderate dystrophic features. These are the first Korean LGMD2B cases with a dysferlin deficiency confirmed by immunocytochemistry. The clinical, pathological, and immunocytochemical findings of the patients with LGMD2B in this study were in accordance with those of other previous reports.

Fig. 1

Muscle specimens of the quadriceps femoris muscle (from patient No. 1) stained by hematoxylin-eosin (A) and modified Gomori Trichrome (B). There were great variation in the size of fibers, fiber splitting with internal nuclei, and clumps of small fibers (×200).

Fig. 2

Immunostaining against α-sarcoglycan (α-SG), β-sarcoglycan (β-SG), caveolin-3 (Cav-3), and β-dystroglycan (β-DG) on the muscle specimen in the four LGMD2B patients by the diaminobenzidine (DAB)-peroxidase method. All four LGMD2B patients showed a normal immunoreactivity against α-sarcoglycan, β-sarcoglycan, caveolin-3, and β-dystroglycan (×200).

Fig. 3

Immunostaining against dysferlin on the muscle specimens from the four LGMD2B patients by a fluorescent isothiocyanate (FITC) technique. Normal control (A) showed a positive immunoreactivity against dysferlin at the sarcolemma. However, all four LGMD2B patients (B-E) showed a complete absence of a reaction against dysferlin at the sarcolemma on the muscle specimen (×200).