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

Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency, which results in the intracellular accumulation of globotriaosylceramide and leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. We report 52- and 55-year-old women with proteinuria and hematuria that were proven to be due to Fabry disease. A gene analysis using PCR direct sequencing confirmed a missense mutation of the GLA (alpha-galactosidase A) gene. Electron microscopy of a kidney biopsy showed lamella inclusion bodies, which are typical findings of Fabry disease. The patients were treated with enzyme replacement therapy as outpatients. They had a reduction in proteinuria and normal renal function.
alpha-Galactosidase* ; Biopsy* ; Enzyme Replacement Therapy ; Fabry Disease* ; Female ; Genes, vif ; Hematuria ; Humans ; Inclusion Bodies ; Kidney* ; Microscopy, Electron ; Middle Aged ; Mutation, Missense ; Outpatients ; Polymerase Chain Reaction ; Proteinuria*

No abstract available.
Biopsy ; DNA Mutational Analysis ; *Diagnostic Errors ; Enzyme Replacement Therapy ; Fabry Disease/complications/*diagnosis/enzymology/genetics ; Genetic Predisposition to Disease ; Glomerulonephritis, IGA/diagnosis/etiology ; Humans ; Male ; Middle Aged ; Mutation ; Phenotype ; Predictive Value of Tests ; Purpura, Schoenlein-Henoch/*diagnosis ; alpha-Galactosidase/genetics/therapeutic use

BACKGROUND AND PURPOSE: The etiology of small fiber neuropathy (SFN) often remains unclear. Since SFN may be the only symptom of late-onset Fabry disease, it may be underdiagnosed in patients with idiopathic polyneuropathy. We aimed to uncover the etiological causes of seemingly idiopathic SFN by applying a focused investigatory procedure, to describe the clinical phenotype of true idiopathic SFN, and to elucidate the possible prevalence of late-onset Fabry disease in these patients. METHODS: Forty-seven adults younger than 60 years with seemingly idiopathic pure or predominantly small fiber sensory neuropathy underwent a standardized focused etiological and clinical investigation. The patients deemed to have true idiopathic SFN underwent genetic analysis of the alpha-galactosidase A gene (GLA) that encodes the enzyme alpha-galactosidase A (Fabry disease). RESULTS: The following etiologies were identified in 12 patients: impaired glucose tolerance (58.3%), diabetes mellitus (16.6%), alcohol abuse (8.3%), mitochondrial disease (8.3%), and hereditary neuropathy (8.3%). Genetic alterations of unknown clinical significance in GLA were detected in 6 of the 29 patients with true idiopathic SFN, but this rate did not differ significantly from that in healthy controls (n=203). None of the patients with genetic alterations in GLA had significant biochemical abnormalities simultaneously in blood, urine, and skin tissue. CONCLUSIONS: A focused investigation may aid in uncovering further etiological factors in patients with seemingly idiopathic SFN, such as impaired glucose tolerance. However, idiopathic SFN in young to middle-aged Swedish patients does not seem to be due to late-onset Fabry disease.
Adult ; Alcoholism ; alpha-Galactosidase ; Diabetes Mellitus ; Erythromelalgia* ; Fabry Disease* ; Glucose ; Humans ; Mitochondrial Diseases ; Phenotype* ; Polyneuropathies ; Prevalence ; Skin

Fabry disease is a progressive X-linked disorder of glycosphingolipid metabolism caused by a deficiency of the alpha-galactosidase lysosomal enzyme. The partial or complete deficiency of the lysosomal enzyme leads to an accumulation of neutral glycosphingolipids in the vascular endothelium and visceral tissues throughout the body. In the heart, glycosphingolipids deposition causes progressive left ventricular hypertrophy (LVH). We report a case of Fabry disease which was suspected based upon two-dimensional echocardiographic finding of LVH. A 44-year-old man was admitted to evaluation of aggravated exertional dyspnea of two weeks duration. He had been diagnosed with end-stage renal disease of unknown etiology at age 41 followed by renal transplantation that year. He had been treated with oral immunosuppressive agents. On hospital day two, transthoracic echocardiography revealed concentric LVH. Left ventricular systolic function was preserved but diastolic dysfunction was present. Fabry disease was confirmed by demonstration of a low plasma alpha-galactosidase A (alpha-Gal A) activity. Analysis of genomic DNA showed alpha-Gal A gene mutation. The patient was diagnosed with Fabry disease.
alpha-Galactosidase ; Cardiomyopathies ; DNA ; Dyspnea ; Echocardiography ; Endothelium, Vascular ; Fabry Disease ; Genes, vif ; Glycosphingolipids ; Heart ; Humans ; Hypertrophy, Left Ventricular ; Immunosuppressive Agents ; Kidney Failure, Chronic ; Kidney Transplantation ; Neutral Glycosphingolipids ; Plasma

OBJECTIVEFabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.

METHODSAll exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed.

RESULTSA unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.

CONCLUSIONThe unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.

Adult ; Fabry Disease ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; alpha-Galactosidase ; genetics

A 28-year-old Asian male was referred for dermatologic evaluation of diffuse bluish-red maculopapules in the lower trunk and genital regions. There was no family history, and with the exception of dispersed skin lesions and hypohidrosis, no other complaints or symptoms were present. Histological evaluation of the skin lesions revealed angiokeratomas. When this combination of clinical and histological findings is observed, Fabry disease is suspected. Biochemical examination performed for definitive diagnosis did not show any activity of the alpha-galactosidase A enzyme. Through identification of a c.182_183ins(GA) mutation of the GLA gene, Fabry disease was diagnosed. However, there was no particular abnormal finding with regard to the evaluation of non-cutaneous manifestations, a symptom that can occur in the progress of this disease. We reported a case of Fabry disease, restricted to the dermatologic presentation, involving a novel frameshift mutation in the GLA gene.
alpha-Galactosidase ; Angiokeratoma ; Asian Continental Ancestry Group ; Fabry Disease ; Frameshift Mutation ; Humans ; Hypohidrosis ; Male ; Skin ; Skin Manifestations

A 28-year-old Asian male was referred for dermatologic evaluation of diffuse bluish-red maculopapules in the lower trunk and genital regions. There was no family history, and with the exception of dispersed skin lesions and hypohidrosis, no other complaints or symptoms were present. Histological evaluation of the skin lesions revealed angiokeratomas. When this combination of clinical and histological findings is observed, Fabry disease is suspected. Biochemical examination performed for definitive diagnosis did not show any activity of the alpha-galactosidase A enzyme. Through identification of a c.182_183ins(GA) mutation of the GLA gene, Fabry disease was diagnosed. However, there was no particular abnormal finding with regard to the evaluation of non-cutaneous manifestations, a symptom that can occur in the progress of this disease. We reported a case of Fabry disease, restricted to the dermatologic presentation, involving a novel frameshift mutation in the GLA gene.
alpha-Galactosidase ; Angiokeratoma ; Asian Continental Ancestry Group ; Fabry Disease ; Frameshift Mutation ; Humans ; Hypohidrosis ; Male ; Skin ; Skin Manifestations

αGal, a xenotransplantations antigen (XTA), can lead to hyper acute reaction (HAR) in xenotransplantation. α-Galactosidase from B. fragilis is a novel galactosidase belong to CAZy GH110 which can clear the terminal αGal from branched and linear oligosaccharides. This study was purposed to investigate the removal effect of a novel α-galactosidase on α-Gal XTA on surface of red blood cells. The αGal XTA from the red blood cells of cattle, pig, dog and rabbit was digested by using recombinant α-galactosidase; the α-Gal antigens on surface of cells was detected by flow cytometry. The results showed that the XTA was disappeared completely or mainly. It is concluded that the novel α-galactosidase is a potential enzyme to remove the XTA on the surface of xenotransplants and can be used to overcome the HAR in xenotransplantation.
Animals ; Antigens, Heterophile ; immunology ; Cattle ; Dogs ; Epitopes ; Erythrocytes ; immunology ; Macaca mulatta ; Mice ; Mice, Inbred BALB C ; Rabbits ; Swine ; Transplantation, Heterologous ; alpha-Galactosidase ; immunology

BACKGROUND: Bovine pericardium is one of the most widely used materials in bioprosthetic heart valves. Immunologic responses have been implicated as potential causes of limited durability of xenogenic valves. This study aimed to determine the effectiveness of decellularization and alpha-galactosidase (alpha-gal) to remove major xenoreactive antigens from xenogenic tissues. MATERIALS AND METHODS: Recombinant Bacteroides thetaiotaomicron (B. thetaiotaomicron) alpha-gal or decellularization, or both were used to remove alpha-gal from bovine pericardium. It was confirmed by alpha-gal-bovine serum albumin-based enzyme-linked immunosorbent assay (ELISA), high-performance anion exchange chromatography, flow cytometry, 3,3'-diaminobenzidine-staining, and lectin-based ELISA. The mechanical properties of bovine pericardium after decellularization or alpha-gal treatment were investigated by tests of tensile-strength, permeability, and compliance. Collagen fiber rearrangement was also evaluated by a 20,000x transmission electron microscope (TEM). RESULTS: Recombinant B. thetaiotaomicron alpha-gal could effectively remove alpha-gal from bovine pericardium B. thetaiotaomicron (0.1 U/mL, pH 7.2) while recombinant human alpha-gal removed it recombinant human alpha-gal (10 U/mL, pH 5.0). There was no difference in the mechanical properties of fresh and recombinant alpha-gal-treated bovine pericardium. Furthermore, the TEM findings demonstrated that recombinant alpha-gal made no difference in the arrangement of collagen fiber bundles with decellularization. CONCLUSION: Recombinant B. thetaiotaomicron alpha-gal effectively removed alpha-gal from bovine pericardium with a small amount under physiological conditions compared to human recombinant alpha-gal, which may alleviate the harmful xenoreactive immunologic responses of alpha-gal. Recombinant alpha-gal treatment had no adverse effects on the mechanical properties of bovine pericardium.
alpha-Galactosidase ; Bacteroides ; Bioprosthesis ; Chromatography ; Collagen ; Compliance ; Electrons ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Flow Cytometry ; Heart Valves ; Humans ; Hydrogen-Ion Concentration ; Pericardium ; Permeability ; Tissue Engineering