M.P.2.01 Late-onset Pompe disease: A report of three cases in Rio Grande do Sul State, Brazil and identification of novel mutations

Pompe disease, rare autosomal recessive disorder caused by deficiency acid alpha-glucosidase (GAA), shows intracellular accumulation of glycogen. The clinical classification includes infantile and late-onset forms of the disease. To describe three cases of late-onset Pompe disease regarding clinical, laboratory, genotype and muscle biopsy aspects. To describe new mutation in two cases. Two male siblings (32/40 years) and one female (23 years) were assessed. Symptoms onset ranged from 12 to 27 years and diagnosis started on average 8.3 years later. The patients showed abnormal spirometry, (noninvasive ventilation more than 12 h/day in two), and one male patient presented spirometric changes before muscle weakness started. Patients showed waddling gait, decreased proximal strength and paravertebral muscle weakness strength, being the female patient the most affected one. The EMG revealed myopathic pattern and CK levels were about eight times normal upper limit. Muscle biopsy (two siblings) showed vacuolar myopathy and glycogen accumulation with positivity for acid phosphatase. The dried blood spot on filter paper to detect GAA activity confirmed diagnoses (mean inhibition GAA was 93.3% and relative ratio acid/neutral GAA activities were more than 47.2%). Genotyping studies revealed common intronic mutation (female) and both siblings present two novel mutations (c.1781G.C,p.Arg594Pro/ c.1941C > G,p.Cys647Trp). Analyses indicated correlation between the disease severity and abnormalities on muscle biopsy. We couldn’t show a linear association between disease severity and the GAA levels. We identified novel mutations in sibling patients. All patients began enzyme replacement therapy (ETR) on January 2007. Considering the therapeutic perspectives by ERT, all adolescent/adult patients presenting pelvic and shoulder girdle muscular weakness should be investigated regarding Pompe disease, mainly if respiratory symptoms are observed.