false
zh-CN,zh-TW,en,fr,de,ja,ko,pt,es,th,vi
Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
Genomic and Biochemical Profile of Pseudodeficienc ...
Genomic and Biochemical Profile of Pseudodeficiency in Lysosomal Storage Disorders
Back to course
Pdf Summary
This study explores the genetic and biochemical profile of pseudodeficiency in four lysosomal storage disorders (LSDs): Pompe disease, Krabbe disease, Mucopolysaccharidosis type I (MPS I), and Fabry disease. Pseudodeficiency refers to reduced enzyme activity in vitro, which can sometimes be indistinguishable from disease-causing enzyme deficiencies. To differentiate between pseudodeficiency and actual disease, genetic sequencing and biomarker analysis are crucial.<br /><br />The study found that none of the cases with pseudodeficiency alleles had enzyme activity within the normal range. However, biomarkers such as psychosine, GAGs, and Lyso-GB3 were elevated in cases with pathogenic alleles. For example, psychosine was significantly elevated in cases with pathogenic GALC alleles, while GAGs were elevated in cases with pathogenic IDUA alleles, and Lyso-GB3 was elevated in cases with pathogenic GLA alleles.<br /><br />The detection rate of pseudodeficiency alleles varied among the different LSDs. GALC and IDUA cases had higher rates of pseudodeficiency allele detection compared to GAA cases. The detection rate of potential-diagnostic/diagnostic variants was higher in males than females for the GLA gene.<br /><br />The study concludes that incorporating biomarker analysis alongside enzyme activity testing can help optimize the laboratory analysis pipeline and reduce the burden on laboratories and clinical management. These findings can help rule out false-positive cases caused by pseudodeficiency, especially in newborn screening programs. Furthermore, understanding the genetic and biochemical profile of pseudodeficiency alleles can contribute to the accurate diagnosis and management of late-onset LSD-related conditions.
Asset Subtitle
Co-Author - Xiangwen Chen-Deutsch, PhD; Presenting Author - Taraka Donti, PhD, FACMG; Co-Author - Zhili Lin, PhD; Co-Author - Christin D. Collins, PhD, FACMG; Co-Author - Madhuri Hedge, Ph.D, FACMG;
Meta Tag
Biochemical genetics
Genetic Testing
Metabolic Disorder
Co-Author
Xiangwen Chen-Deutsch, PhD
Co-Author
Zhili Lin, PhD
Co-Author
Christin D. Collins, PhD, FACMG
Co-Author
Madhuri Hedge, Ph.D, FACMG
Presenting Author
Taraka Donti, PhD, FACMG
Keywords
pseudodeficiency
lysosomal storage disorders
enzyme activity
genetic sequencing
biomarker analysis
psychosine
GAGs
Lyso-GB3
detection rate
late-onset LSD-related conditions
© 2025 American College of Medical Genetics and Genomics. All rights reserved.
×