(RS13) Clinical and Molecular Spectrum of Patients with Infantile-Onset Pompe Disease in Malaysia

Introduction:

Pompe disease is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to deficiency of the enzyme alpha-glucosidase (GAA). Infantile-onset Pompe disease (IOPD) patients present within the first year of life with rapidly progressive cardiomyopathy. Untreated patients often die before the age of 2 years from cardiorespiratory failure. Early treatment with enzyme replacement therapy (ERT) significantly improves survival.

Results:

Seventeen patients were diagnosed with IOPD, of which 16 received ERT. The median age of presentation was three months and median age of diagnosis was six months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (75%). Fifteen different mutations in the GAA gene were found in our patients, with three novel mutations (c.1552-14_1552-1del, exon 2-3 deletion and exon 6-10 deletion). The most common mutation was the c.1935C>A, with an allele frequency of 33%. Overall survival was 29% and ventilation free survival 17.6%.

Discussion/Conclusion:

Malaysian IOPD patients presented with classic features of IOPD. Our mutation spectrum is similar to that described in East Asian IOPD patients. Early diagnosis and initiation of treatment is pivotal to achieving better long term outcomes.