Molecular Diagnosis of Pompe Disease in the Genomic Era: Correlation with Acid Alpha-Glucosidase Activity in Dried Blood Spots

Journal of Clinical Medicine

Bojana Rakic¹  Sébastien Lévesque²  Serge Gravel²  Fanny Thuriot²  Elaine Gravel²  Paula J. Waters²  Jorge Ganopolsky³  Katherine Hodson³ 

[1] BC Children’s Hospital, Vancouver, BC V6H 3N1, Canada;Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, Canada;Dynacare, Laval, QC H7L 4S3, Canada;

关键词: Pompe disease;    gene panel sequencing;    alpha-glucosidase;    GAA;    dried-blood spots;   

DOI  :  10.3390/jcm10173868

来源: DOAJ

【 摘 要 】

Measurement of alpha-glucosidase activity on dried blood spots has been the main method to screen for Pompe disease, but a paradigm shift has been observed in recent years with the incorporation of gene panels and exome sequencing in molecular diagnostic laboratories. An 89-gene panel has been available to Canadian physicians since 2017 and was analyzed in 2030 patients with a suspected muscle disease. Acid alpha-glucosidase activity was measured in parallel in dried blood spots from 1430 patients. Pompe disease was diagnosed in 14 patients, representing 0.69% of our cohort. In 7 other patients, low enzyme activities overlapping those of Pompe disease cases were attributable to the presence of pseudodeficiency alleles. Only two other patients had enzymatic activity in the Pompe disease range, and a single heterozygous pathogenic variant was identified. It is possible that a second variant could have been missed; we suggest that RNA analysis should be considered in such cases. With gene panel testing increasingly being performed as a first-tier analysis of patients with suspected muscle disorders, our study supports the relevance of performing reflex enzymatic activity assay in selected patients, such as those with a single GAA variant identified and those in whom the observed genotype is of uncertain clinical significance.

【 授权许可】

Unknown