Post-mortem diagnosis of Pompe disease by exome sequencing in a Moroccan family: a case report

Abstract

BackgroundPompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy. Its prevalence ranges between 1/9000 and 1/40,000. It is caused by compound heterozygous or homozygous mutations in the GAA gene, which encodes for the lysosomal enzyme alpha-glucosidase, required for the degrading of lysosomal glycogen.Case presentationIn this study, we report the case of a Moroccan consanguineous family with hypertrophic cardiomyopathy and sudden cardiac deaths at an early age; our patient was a 7-month-old Moroccan girl. Whole exome sequencing identified the deleterious homozygous mutation c.236_246delCCACACAGTGC (p.Pro79ArgfsX13) of GAA gene leading to a post-mortem diagnosis of Pompe disease.ConclusionThe identification of the genetic substrate in our patient, the daughter, confirmed the clinical diagnosis of Pompe disease and allowed us to provide appropriate genetic counseling to the family for future pregnancies.

The Novel Compound Heterozygous Mutations of GAA Gene in Mainland Chinese Patient with Classic Infantile-Onset Pompe Disease

“…Moreover, Adadi et al demonstrated the use of exome sequencing as a systematic and unbiased diagnostic tool in a pediatric case with hypertrophic cardiomyopathy. 12) Screening in healthy newborns is now possible by demonstrating low GAA activity in DBS complemented by DNA mutation analysis. Newborn screening is the best method for early diagnosis of PD, and at present, newborn screening has been carried out in Taiwan and parts of the United States, which is of great significance for the prognosis of IOPD patients.…”