PP09.12 – 3028: Broad spectrum of c.2015 G>A mutation in GAA gene manifesting as mild infantile variant of Pompe disease in Jordanian patients

Abstract

Objective A wide spectrum of Pompe disease exists from the infantile form to a milder juvenile or adult form. The clinical heterogeneity primarily relates to the occurrence of different mutations that lead to a different rate of lysosomal glycogen accumulation and non genetic factors that are thought to modulate the disease phenotypes. Methods We describe two unrelated families from Jordan presenting with the infantile variant form of Pompe disease sharing the same homozygous mutation c.2015 G>A in exon 14. Previously this mutation was described in juvenile onset cases. Results The first family consisted of two female siblings (5.5 and 3.5 years of age) born to first degree cousins of Muslim descent. The elder one presented between 3–6 months of age with marked hypotonia, hypertrophic cardiomyopathy, proximal muscle weakness, motor delay and no DTR's. She was started on enzyme replacement therapy at 24 months of age, walked independently at 27 months. Currently she has a nasal speech, muscle weakness and mild cardiomyopathy. Her younger sister, presented at 3 months with mild hypotonia, motor delay and hepatomegaly. She started ERT at 6 months and currently her neurological examination is normal. The second patient is a 5-year-old boy who presented with hypertrophic cardiomyopathy, hypotonia and an enlarged tongue. His parents are first degree cousins. Two siblings died before the age of one month due to heart failure; He started ERT at 14 months of age, walked independently at 18 months and follow-up echocardiography studies improved markedly. Currently he has a nasal speech, articulation disorder and otherwise no muscle weakness. Conclusion Our cases confirm the phenotypic variability among patients, even carrying the same genotype. Two patients, for whom ERT was commenced later, suffer from nasal speech and severe articulation disorder in spite of improved cardiac and motor function.