Sarcoglycanopathies: A clinico-pathological study

Background : Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders characterized by limb girdle weakness. There are no clear clinical features that distinguish various types of LGMD. Materials and Methods : We studied 26 patients with chronic progressive weakness in limb girdle distribution without early facial involvement with muscle biopsies suggestive of dystrophy/myopathy and positive for dystrophin antibodies. Immunohistochemistry studies of muscle biopsies were done on all patients to classify different types of sarcoglycanopathies. Results : The mean age of presentation was in the third decade. There were 14 male and 12 female patients. The common pattern of inheritance was autosomal recessive, seen in 53.8%. The more frequent type of LGMD was sarcoglycanopathy (SGP) (53.8%). Amongst the SGPs, alpha-SGP (26.9%) was the most common followed by beta-SGP (15.3%), gamma-SGP (3.8%) and delta-SGP (7.6%). Calf hypertrophy was noted in 53.5% of LGMD and 57.1% of SGPs, extensor digitorum brevis hypertrophy in 42% of LGMD and 35.7% of SGPs, winging of scapula in 39.2% of the LGMD group and 35.7% of the SGPs, valley sign in 28.5% of the LGMD group and 21.4% of the SGPs. Hip abductor sign was positive in 71.4% of LGMD and 64.2% of SGPs. Differential weakness of knee flexors was more common in SGP (57.1%). The mean creatine phosphokinase (CK) value was 2519IU/L and was elevated in 92.8% patients. Muscle biopsy showed a dystrophic pattern in 75% of LGMD and a myopathic pattern in the remaining. Symptomatic cardiac involvement was seen in one patient. ECG changes were seen in 44% of LGMD patients and 50% of the SGP. The common changes noted were T wave inversion in V1, V2 (16%), left ventricular hypertrophy LVH (12%) and right bundle branch block (RBBB) in 12% of the LGMD group. Conclusion: Sarcoglycanopathy is a more frequent form of LGMD whereas alpha type is the most common among the SGP. The four types of SGP do not differ in the pattern of muscle involvement. A relatively earlier onset, selective weakness of knee flexors and a very high CK may help differentiate SGP from other forms of LGMD. Immunohistochemistry is very useful in classifying the different types of LGMD prior to genetic analysis