A post-mortem diagnosis of infantile-onset Pompe disease in an Iranian family

Backgrounds: Pompe disease, also called glycogen storage disease type II, is a kind oflysosomal storage disease causes glycogen storage in body cells especially in heart, liver andmuscle. The most important features of disease are HCM (hypertrophic cardiomyopathy),respiratory distress and failure to thrive. The frequency of Pompe disease is between ۱/۹۰۰۰ and۱/۴۰,۰۰۰. Pompe disease has autosomal recessive inheritance and caused by mutations in GAAgene that codes alpha-glucosidase (α-۱,۴-glucosidase). The role of this enzyme is degradation ofglycogen in lysosome. In the present study, we are reporting a case of infantile-onset Pompedisease in an ۱۸ months’ infant.Materials and Methods: The case is an ۱۸ months’ infant with the symptoms of macroglossiaand heart disorders. He was clinically diagnosed for Pompe disease. Metabolic enzyme testingwas positive for him but negative for his parents. Sometimes later the infant died. The parents’marriage was not consanguineous. The parent’s blood specimens were collected and DNAextraction was done. Whole exome sequencing (WES) using Illumina HiSeq۴۰۰۰ platform wasperformed.Results: The c.۸۹۶T>C (p. Leu۲۹۹Pro) and c.۲۰۱۵G>A (p. Arg۶۷۲Gln) mutations in GAA genewere found in WES analysis in mother and father, respectively. According to American Collegeof Medical Genetics (ACMG), the variants were pathogenic. Both parents were career and thedeceased infant was compound heterozygous for GAA gene.Conclusion: In this case, WES as a powerful diagnostic tool helped us to confirm the clinicaldiagnosis of Pompe disease. PND (prenatal diagnosis) for future pregnancies and geneticcounseling for other members of family were suggested.

Keywords:

Pompe disease , WES , GAA gene , Compound heterozygous , Post-mortem