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.
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*

Humans ; Fabry Disease/therapy* ; Hypertrophy, Left Ventricular/diagnosis* ; Diagnosis, Differential

Humans ; Fabry Disease/therapy* ; Hypertrophy, Left Ventricular/diagnosis* ; Diagnosis, Differential

Humans ; Fabry Disease/therapy*

Child ; Humans ; Gaucher Disease/therapy*

Fabry disease is a rare X-linked hereditary condition caused by mutations in the α-galactosidase A (GLA) gene, resulting in decreased α-GAL A enzyme activity. The clinical manifestations of Fabry disease are diverse, which leads to delays in diagnosis and treatment, thereby increasing the disease burden for patients and their families. Given its characteristics, multidisciplinary treatment (MDT) is critical for the long-term management of Fabry disease, and should include nephrology departments, cardiovascular departments, neurology departments, and pediatric department, among others. This study focuses on early screening for Fabry disease, the indication for initiating enzyme replacement therapy, pre-treatment evaluation, and monitoring to provide practical guidance for Chinese clinicians.
Child ; Humans ; Fabry Disease/drug therapy* ; alpha-Galactosidase/therapeutic use* ; Mutation ; Enzyme Replacement Therapy

Humans ; Gaucher Disease/pathology*

Child ; Consensus ; Gaucher Disease/therapy* ; Humans

OBJECTIVE: To delineate the clinical and genetic features of a Chinese boy suspected for Niemann-Pick disease type C. METHODS: The patient underwent clinical examination and was subjected to next generation sequencing. Suspected mutations were validated by Sanger sequencing. Potential impact of the novel mutation was predicted by SIFT, PolyPhen-2 and MutationTaster software. RESULTS: The child has featured hepatosplenomegaly, increased direct bilirubin, jaundiced skin and liver damage. DNA sequencing showed that he has carried compound heterozygous mutations of NPC1 gene, namely c.2728Gc.269C>G (p.P90R), which were inherited from his mother and father, respectively. The c.2728G>A (p.G910S) mutation was previously reported, while the c.269C>G (p.P90R) was a novel mutation. CONCLUSION The child has suffered from Niemann-Pick disease type C due to mutations of NPC1 gene. Above finding has enriched the spectrum of NPC1 mutations and provided a basis for genetic counseling and prenatal diagnosis.
Asian Continental Ancestry Group ; Bilirubin ; Carrier Proteins ; genetics ; Child ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Mutation ; Niemann-Pick Disease, Type C ; genetics

Acute Disease ; Adult ; Cerebral Infarction ; diagnosis ; diagnostic imaging ; Fabry Disease ; diagnosis ; diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male