Pompe disease, also known as glycogen storage disease (GSD) and as lysosomal storage disease, is an autosomal recessive disorder with an estimated incidence of between 1/9000 and 1/40,000 [
1‐
3]. It is caused by compound heterozygous or homozygous mutations in the
GAA gene, which encodes the lysosomal enzyme alpha-glucosidase (α-1,4-glucosidase) that is required for the degrading of lysosomal glycogen. Deficiency of α-1,4-glucosidase causes generalized accumulation of lysosomal glycogen in various tissues especially in the heart, skeletal system, and nervous system [
4]. The clinical presentation varies widely with respect to age of onset, organ involvement, severity, and rate of progression. Infantile-onset Pompe disease presents in the first 2 months of life with hypotonia, feeding difficulties, failure to thrive, respiratory distress, hypertrophic cardiomyopathy (HCM), and hearing loss. Without treatment by enzyme replacement therapy (ERT), death commonly occurs in the first year of life from progressive left ventricular outflow obstruction [
4,
5]. The late-onset form (that is, childhood, juvenile, and adult-onset) is characterized mainly by progressive muscle weakness, swallowing difficulties, and respiratory insufficiency at a slower rate. Early initiation of ERT may reduce cardiac mass and improve the ejection fraction [
6].
Here we present a family with HCM and sudden cardiac deaths in multiple siblings in whom genetic testing using whole exome sequencing (WES) established a post-mortem diagnosis of Pompe disease.