Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants
Open Access
- 27 January 2021
- journal article
- Published by Wiley in JIMD Reports
- Vol. 59 (1), 60-68
- https://doi.org/10.1002/jmd2.12201
Abstract
Population studies point to regional and ethnicity‐specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban‐dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large‐scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns. Fluorimetric enzyme assays for GD, PD, and FD were performed on dried blood spots. Targeted gene sequencing was performed on samples that showed significantly lower enzyme activities ( T; p.R168L, (c) c.1985del. Regarding FD, two subjects had pathogenic GLA mutations, and four had single nucleotide polymorphisms in the 5'UTR, previously implicated in modulating gene expression. The findings highlight a higher incidence of abnormal enzyme levels and pathogenic mutations in the target population reflecting ancestry‐based specific genotype and phenotype variations.Funding Information
- National Center for Advancing Translational Sciences (UL1‐TR001409, UL1TR000101)
- Pfizer (WI194030)
- Shire (IIR‐USA‐000892)
This publication has 26 references indexed in Scilit:
- Novel GAA mutations in patients with Pompe diseaseGene, 2015
- The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry diseaseBest Practice & Research Clinical Endocrinology & Metabolism, 2015
- Detecting multiple lysosomal storage diseases by tandem mass spectrometry — A national newborn screening program in TaiwanClinica Chimica Acta; International Journal of Clinical Chemistry, 2014
- Gaucher Disease and Its Treatment OptionsAnnals of Pharmacotherapy, 2013
- Renal complications of Fabry disease in children.Pediatric Nephrology, 2012
- Optimal therapy in Gaucher diseaseTherapeutics and Clinical Risk Management, 2010
- Phenotype, diagnosis, and treatment of Gaucher's diseaseThe Lancet, 2008
- Late onset Pompe disease: Clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patientsNeuromuscular Disorders, 2007
- Fabry disease: a reviewJoint Bone Spine, 2004
- Lysosomal storage disorders: emerging therapeutic options require early diagnosisEuropean Journal of Pediatrics, 2003