Cargando…

Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series

AIMS: Fabry disease (FD) is an X‐linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi‐organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum o...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Xin, Li, Hezhi, Liao, Hongtao, Zhan, Xianzhang, Zhong, Zhian, Zhang, Qianhuan, Liu, Lie, Liang, Yuanhong, Deng, Hai, Fang, Xianhong, Xue, Yumei, Wu, Shulin, Liu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712914/
https://www.ncbi.nlm.nih.gov/pubmed/34704396
http://dx.doi.org/10.1002/ehf2.13638
_version_ 1784623663052488704
author Chen, Xin
Li, Hezhi
Liao, Hongtao
Zhan, Xianzhang
Zhong, Zhian
Zhang, Qianhuan
Liu, Lie
Liang, Yuanhong
Deng, Hai
Fang, Xianhong
Xue, Yumei
Wu, Shulin
Liu, Yang
author_facet Chen, Xin
Li, Hezhi
Liao, Hongtao
Zhan, Xianzhang
Zhong, Zhian
Zhang, Qianhuan
Liu, Lie
Liang, Yuanhong
Deng, Hai
Fang, Xianhong
Xue, Yumei
Wu, Shulin
Liu, Yang
author_sort Chen, Xin
collection PubMed
description AIMS: Fabry disease (FD) is an X‐linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi‐organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families. METHODS AND RESULTS: Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G > A, c.811G > A, c.950T > C), 1 novel missense mutation (c.37G > C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre‐excitation occurred in 80% (4/5) of men and 16.7% (1/6) of women. Six patients (6/14, 42.9%) had chronic kidney disease with decreased renal function and all were male (6/7, 85.7%). Six patients presented with acroparesthesia, hypohidrosis, or both. Three female patients and two male patients experienced sudden death, and one male patient with the mutation (c.128G > A) died of progressive heart failure, between 41 and 66 years of age. CONCLUSIONS: We reported five unrelated families of FD with different GLA mutations. Clinical manifestations were highly heterogeneous between male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long‐term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD.
format Online
Article
Text
id pubmed-8712914
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-87129142022-01-04 Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series Chen, Xin Li, Hezhi Liao, Hongtao Zhan, Xianzhang Zhong, Zhian Zhang, Qianhuan Liu, Lie Liang, Yuanhong Deng, Hai Fang, Xianhong Xue, Yumei Wu, Shulin Liu, Yang ESC Heart Fail Original Articles AIMS: Fabry disease (FD) is an X‐linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi‐organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families. METHODS AND RESULTS: Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G > A, c.811G > A, c.950T > C), 1 novel missense mutation (c.37G > C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre‐excitation occurred in 80% (4/5) of men and 16.7% (1/6) of women. Six patients (6/14, 42.9%) had chronic kidney disease with decreased renal function and all were male (6/7, 85.7%). Six patients presented with acroparesthesia, hypohidrosis, or both. Three female patients and two male patients experienced sudden death, and one male patient with the mutation (c.128G > A) died of progressive heart failure, between 41 and 66 years of age. CONCLUSIONS: We reported five unrelated families of FD with different GLA mutations. Clinical manifestations were highly heterogeneous between male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long‐term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD. John Wiley and Sons Inc. 2021-10-26 /pmc/articles/PMC8712914/ /pubmed/34704396 http://dx.doi.org/10.1002/ehf2.13638 Text en © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Chen, Xin
Li, Hezhi
Liao, Hongtao
Zhan, Xianzhang
Zhong, Zhian
Zhang, Qianhuan
Liu, Lie
Liang, Yuanhong
Deng, Hai
Fang, Xianhong
Xue, Yumei
Wu, Shulin
Liu, Yang
Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title_full Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title_fullStr Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title_full_unstemmed Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title_short Clinical and genetic spectrum in Chinese families with Fabry disease: a single‐centre case series
title_sort clinical and genetic spectrum in chinese families with fabry disease: a single‐centre case series
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712914/
https://www.ncbi.nlm.nih.gov/pubmed/34704396
http://dx.doi.org/10.1002/ehf2.13638
work_keys_str_mv AT chenxin clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT lihezhi clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT liaohongtao clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT zhanxianzhang clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT zhongzhian clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT zhangqianhuan clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT liulie clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT liangyuanhong clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT denghai clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT fangxianhong clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT xueyumei clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT wushulin clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries
AT liuyang clinicalandgeneticspectruminchinesefamilieswithfabrydiseaseasinglecentrecaseseries