Publication:
Genotype-phenotype correlation of 17 cases of Pompe disease in Spanish patients and identification of 4 novel GAA variants.

Loading...
Thumbnail Image

Date

2021-05-21

Authors

Hernández-Arévalo, Paula
Santotoribio, José D
Delarosa-Rodríguez, Rocío
González-Meneses, Antonio
García-Morillo, Salvador
Jiménez-Arriscado, Pilar
Guerrero, Juan M
Macher, Hada C

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

Pompe disease (PD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the acid α-glucosidase gene (GAA) that produces defects in the lysosomal acid α-1,4-glucosidase. We aimed to identify genetic variations and clinical features in Spanish subjects to establish genotype-phenotype correlation. A total of 2637 samples of patients who showed symptoms or susceptible signs of PD were enrolled in this observational study. Enzymatic activity was detected by fluorometric techniques and the genetic study was carried out using Next-Generation Sequencing. Fourteen different variants from 17 diagnosed patients were identified, seven males and nine females with LOPD (mean age 36.07, SD 20.57, range 7-64) and a 2-day-old boy with IOPD, four genetic variants had not been described in the literature previously, including a homozygous variant. In all of them α-glucosidase activity was decreased. Muscle weakness, respiratory distress, exercise intolerance, hypotonia, dysphagia and myalgia were commonly observed in patients. This study report four new genetic variants that contribute to the pathogenic variants spectrum of the GAA gene. We confirm that patients in Spain have a characteristic profile of a European population, with c.-32-13T>G being the most prevalent variant. Furthermore, it was confirmed that the c.236_246delCCACACAGTGC pathogenic variant in homozygosity is associated with early disease and a worse prognosis.

Description

MeSH Terms

Adult
Female
Genetic Association Studies
Glycogen Storage Disease Type II
Homozygote
Humans
Male
Spain
alpha-Glucosidases

DeCS Terms

CIE Terms

Keywords

Alpha-glucosidase enzyme, GAA gene, Genotype–phenotype correlation, Pompe disease

Citation