P.226 - Late-onset limb-girdle myopathy with oculobulbar signs and rimmed vacuoles associated with a novel Pompe disease mutation

Abstract

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by acid alfa-glucosidase (GAA) deficiency. Late-onset phenotype is heterogeneous, and it may include ptosis and/or bulbar weakness. Since 2006 enzyme replacement therapy with alglucosidase alfa has become available with the best benefit depending on residual muscle function. Therefore, its prompt diagnosis has become more noteworthy. We describe a 50-year-old Portuguese woman, which presented with slowly progressive speech slurring and limb-girdle muscle weakness for the previous 25 years. In the last 10 years she also complained of progressive left eyelid drop. No diplopia or dysphagia was present. There was no fatigability or diurnal fluctuation in symptoms. Her medical and familial history was unremarkable. Neurological examination disclosed left ptosis, moderate tongue atrophy and weakness, slight dysarthria and severe limb-girdle muscle weakness. A mildly restrictive respiratory pattern was disclosed on pulmonary function tests. There was no heart involvement. Nerve conduction studies were normal. Needle electromyography disclosed myopathic potentials associated with fibrillation potentials and positive sharp waves. Repetitive nerve stimulation was unremarkable. Serum creatine kinase was mildly elevated (648–881 UI/L). Muscle biopsy showed myopathic changes with some rimmed vacuoles. There was no excessive glycogen accumulation seen with PAS and by electron microscopy (EM). There were no filament inclusions under EM. A reduced GAA enzyme activity (1.58 pmol/h/punction; normal >4.51) was disclosed on dried blood spot analysis. Sequence analysis of the GAA gene revealed a novel pathological mutation in compound heterozygosity [c.-32-13T > G/c.2319C > G(p.Y773*)]. Six months after enzyme replacement therapy, ptosis improved and respiratory function remained stable. This case highlights the need for a high index of suspicion for PD in adult patients with unexplained oculobulbar and limb-girdle muscle weakness, even if the muscle biopsy features are completely atypical.