Correlation of enzyme activities and genotype with clinical manifestations in Chinese patients of different sexes with classical and late-onset Fabry disease.
10.1007/s11684-025-1131-9
- Author:
Wenkai GUO
1
;
Yuansheng XIE
2
;
Pengcheng JI
3
;
Qinggang LI
3
;
Peng WANG
3
;
Guangyan CAI
3
;
Xiangmei CHEN
3
Author Information
1. School of Medicine, Nankai University, Tianjin, 300071, China.
2. School of Medicine, Nankai University, Tianjin, 300071, China. xieyuansn@hotmail.com.
3. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (zyyzdxk-2023310), Beijing, 100853, China.
- Publication Type:Journal Article
- Keywords:
GLA;
Fabry disease;
classical phenotype;
male;
α-galactosidase A
- MeSH:
Adolescent;
Adult;
Aged;
Female;
Humans;
Male;
Middle Aged;
Young Adult;
Age of Onset;
alpha-Galactosidase/metabolism*;
China;
Fabry Disease/enzymology*;
Genotype;
Mutation;
Phenotype;
Sex Factors;
East Asian People/genetics*
- From:
Frontiers of Medicine
2025;19(3):523-537
- CountryChina
- Language:English
-
Abstract:
Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
