128 Variety is the splice of life

Case 1: A 42-year-old female presented with progressive exertional breathlessness over 2 years. She was breathless at rest and had bilateral Trendelenburg signs. Pulmonary function testing demonstrated a restrictive defect. Serum CK was elevated at 300. EMG demonstrated myotonia. We considered a wide differential, but a very low alpha glucosidase level led to genetic testing revealing GAA heterozygosity (c.-32–13T>G and c.1528G>A; p.(Trp516*) variants), confirming Pompe disease.Case 2: A 35-year-old female presented with a 20-year history of arm and leg weakness. Examination revealed proximal weakness affecting all four limbs but no respiratory involvement. Investigations dem- onstrated a raised CK of 1,000. Neurophysiology confirmed myopathic changes. An alpha glucosidase level was low on two occasions. Genetic testing confirmed GAA heterozygosity: (c.-32–13T>G variant and GAA exon 18 deletion) confirming Pompe disease.Pompe disease is an autosomal recessive condition caused by mutations in the GAA gene. Enzyme deficiency leads to impaired glycogen breakdown, with subsequent body tissue accumulation. GSD-II may present with varying phenotypes which are influenced by genotypic variations and level of enzyme activity, as these cases demonstrate. Diagnosis is important as enzyme replacement therapy is available. The clue is a low alpha-glucosidase level, a simple but crucial test to perform.kawknight@gmail.com89