2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Correlation of Alpha-glucosidase Activity with Genotype: Retrospective Review of Infants Tested Following an Abnormal Newborn Screen

Correlation of Alpha-glucosidase Activity with Genotype: Retrospective Review of Infants Tested Following an Abnormal Newborn Screen

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Pdf Summary

Pompe disease is a genetic disorder caused by a deficiency of the alpha-glucosidase (GAA) enzyme. It has two subtypes - infantile and late onset, with varying symptoms and severity. The aim of this study was to evaluate and characterize the variability of GAA enzyme activity in different genotypes. The researchers tested dried blood spot samples for enzyme activity using a fluorescent substrate. They also performed gene sequencing to identify pathogenic variants in GAA. The study included data from 249 samples, with complete genotype and enzyme activity data for 96 individuals. Among them, 15 were diagnosed with Pompe disease, with 3 cases of infantile Pompe and 12 cases of late-onset Pompe. The study highlighted the challenges in diagnosing Pompe disease, including the presence of pseudodeficiency variants and variable symptoms. The researchers emphasized the importance of DNA sequencing in interpreting biochemical findings. The study also revealed that differentiating true carriers from pseudodeficiency alleles was challenging. They found that enzyme activity levels were highly variable among carriers and individuals with homozygous pseudodeficiency alleles. Infantile Pompe cases had enzyme activity below the normal range, regardless of age at the time of sample collection. Early and accurate diagnosis of Pompe disease is crucial, especially with the development of new therapeutics. The study also mentioned the implementation of newborn screening for Pompe disease in Washington state, which has identified asymptomatic individuals with abnormal enzyme activity and GAA variants. Pseudodeficiency alleles, which do not cause disease but affect enzyme activity measurement, were also discussed. The authors suggested exploring alternative markers and substrates to improve enzyme activity measurements and communicating the results to healthcare providers and genetic counselors for a better understanding of the complexity of Pompe disease.

Asset Subtitle

Co-Author - Anna I. Scott, PhD, FACMG; Presenting Author - Brenna M. Boyd, MA;

Meta Tag

Biochemical genetics

Genotype-Phenotype Correlations

Lysosomal Diseases

Metabolic Disorder

Phenotype

Co-Author Anna I. Scott, PhD, FACMG

Presenting Author Brenna M. Boyd, MA

Keywords

Pompe disease

genetic disorder

alpha-glucosidase enzyme

GAA enzyme activity

gene sequencing

diagnosis challenges

enzyme activity levels

pseudodeficiency alleles

newborn screening

therapeutics development