Gamma-sarcoglycanopathy (LGMDR5): clinical and genetic study of a pediatric Tunisian cohort

Background: Limb-girdle muscular dystrophy type R5 (LGMDR5) is an autosomal-recessive disorder caused by mutations in gamma-sarcoglycan encoding gene. It is characterized by childhood onset of progressive muscular dystrophy. It is frequent in North African populations. Objective: To determine the clinical and genetic characteristics of a Tunisian series of LGMDR5. Methods: retrospective study from 2012 to 2021 collecting demographic, clinical, biological and genetic data of patients with genetically confirmed LGMDR5. Results: 11 boys and 13 girls from 18 families with a mean age of 7.1 years were included. Consanguinity was noted in 17 families. Familial history of similar case was noted in 8 families. Motor milestones were normal (100%). The mean age of onset was 3.7 years. The most frequent inaugural symptoms were difficulties to run and to climb stairs. Clinical examination revealed proximal weakness that was more apparent in pelvic girdle muscles (100%) and calf hypertrophy (83%). Cognitive impairment was observed in 12.5% of patients. Serum creatine kinase levels ranged from 2280 to 18461 U/L. High levels of transaminase was observed (100%). Electromyography showed myogenic pattern (100%). The homozygous c.525delT mutation in the SGCG gene was found in 100% of patients. Steroids were prescribed at the dose of 0.75mg/kg/d in 83% of patients. Six patients (25%) were wheelchair-bound at a mean age of 11.7 years. Respiratory involvement was reported in 12.5% of patients. Conclusion: Our study highlights the recurrent founder mutation in the Tunisian population. Targeted mutational research in the LGMDR5 will enable early diagnosis and facilitate genetic counseling.
Keywords: LGMDR5, muscular, dystrophy, genetic