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Frequency of Fabry disease in a juvenile idiopathic arthritis cohort

BACKGROUND: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including i...

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Autores principales: Paim-Marques, Luciana, Cavalcante, Amanda Virginia, Verçosa, Islane, Carneiro, Paula, Souto-Maior, Marcia, Marques, Erlane, Appenzeller, Simone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199813/
https://www.ncbi.nlm.nih.gov/pubmed/34118938
http://dx.doi.org/10.1186/s12969-021-00563-9
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author Paim-Marques, Luciana
Cavalcante, Amanda Virginia
Verçosa, Islane
Carneiro, Paula
Souto-Maior, Marcia
Marques, Erlane
Appenzeller, Simone
author_facet Paim-Marques, Luciana
Cavalcante, Amanda Virginia
Verçosa, Islane
Carneiro, Paula
Souto-Maior, Marcia
Marques, Erlane
Appenzeller, Simone
author_sort Paim-Marques, Luciana
collection PubMed
description BACKGROUND: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including in the musculoskeletal system. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients is unknown. OBJECTIVE: This study aimed to identify the frequency of FD in a JIA cohort, characterizing early clinical symptoms, enzyme titers, and GLA genotyping. METHODS: Children with JIA followed in a tertiary Children Hospital cohort were selected. Clinical, laboratory and familiar information were recorded. Molecular genetic testing to detect GLA gene mutations was performed in girls and enzymatic analysis in boys. RESULTS: In 89 patients (56.2% female, age at disease onset: 8.93 ± 4.35 years), one male (1.12%) patient presented pathogenic mutation in GLA gene, c.1244 T > C p.L415P, one female patient had a variant of uncertain significance c.38C > T (p.Ala13Val). Three additional (3.4%) patients had the enzymatic activity of alpha-galactosidase slightly decreased. We observed the presence of intronic variants in 44.44% of patients in our cohort: c.1000-22C > T; c.370-81_-77del; c.640-16A > G; c.10C > T; c.548-125C > G and c.-12G > A. These variants and their combination were associated with clinical symptoms in our cohort. CONCLUSIONS: The incidence of FD in our cohort was 1.12%. Intronic variants were associated with symptoms previously described in the literature. Screening for FD in JIA may be a reasonable strategy for those with an atypical pattern of pain.
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spelling pubmed-81998132021-06-15 Frequency of Fabry disease in a juvenile idiopathic arthritis cohort Paim-Marques, Luciana Cavalcante, Amanda Virginia Verçosa, Islane Carneiro, Paula Souto-Maior, Marcia Marques, Erlane Appenzeller, Simone Pediatr Rheumatol Online J Research Article BACKGROUND: Fabry disease (FD) is a rare, X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (⍺-GalA). During childhood, classic FD symptomatology is rare. The majority of children may show non-specific symptoms, including in the musculoskeletal system. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients is unknown. OBJECTIVE: This study aimed to identify the frequency of FD in a JIA cohort, characterizing early clinical symptoms, enzyme titers, and GLA genotyping. METHODS: Children with JIA followed in a tertiary Children Hospital cohort were selected. Clinical, laboratory and familiar information were recorded. Molecular genetic testing to detect GLA gene mutations was performed in girls and enzymatic analysis in boys. RESULTS: In 89 patients (56.2% female, age at disease onset: 8.93 ± 4.35 years), one male (1.12%) patient presented pathogenic mutation in GLA gene, c.1244 T > C p.L415P, one female patient had a variant of uncertain significance c.38C > T (p.Ala13Val). Three additional (3.4%) patients had the enzymatic activity of alpha-galactosidase slightly decreased. We observed the presence of intronic variants in 44.44% of patients in our cohort: c.1000-22C > T; c.370-81_-77del; c.640-16A > G; c.10C > T; c.548-125C > G and c.-12G > A. These variants and their combination were associated with clinical symptoms in our cohort. CONCLUSIONS: The incidence of FD in our cohort was 1.12%. Intronic variants were associated with symptoms previously described in the literature. Screening for FD in JIA may be a reasonable strategy for those with an atypical pattern of pain. BioMed Central 2021-06-12 /pmc/articles/PMC8199813/ /pubmed/34118938 http://dx.doi.org/10.1186/s12969-021-00563-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Paim-Marques, Luciana
Cavalcante, Amanda Virginia
Verçosa, Islane
Carneiro, Paula
Souto-Maior, Marcia
Marques, Erlane
Appenzeller, Simone
Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title_full Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title_fullStr Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title_full_unstemmed Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title_short Frequency of Fabry disease in a juvenile idiopathic arthritis cohort
title_sort frequency of fabry disease in a juvenile idiopathic arthritis cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199813/
https://www.ncbi.nlm.nih.gov/pubmed/34118938
http://dx.doi.org/10.1186/s12969-021-00563-9
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