Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a mutation in the gene encoding the alpha-galactosidase A (GLA) enzyme. We report two cases of Fabry disease in a 12-year-old boy who had acroparesthesia and in his elder brother with milder symptoms who were diagnosed by GLA activity assays and the presence of the GLA gene mutation.
alpha-Galactosidase ; Child ; Enzyme Replacement Therapy ; Fabry Disease ; Humans ; Siblings

PURPOSE: The purpose of this study is to report the genetic diagnosis of nine cases of Fabry in one family, either as carriers or patients. METHODS: We conducted analysis of the alpha-galactosidase A gene and ophthalmologic examination of family members of a patient diagnosed with Fabry disease. RESULTS: Our patient, his brother, and two male cousins had Fabry disease; his mother, three aunts, and his female cousin were Fabry carriers. Genetic study revealed deletion mutation (1235-1236delCT) at the alpha-galactosidase A gene in all subjects. Ophthalmologic examination detected whirl-like corneal opacity in all subjects, which is a typical characteristic of Fabry disease.
alpha-Galactosidase ; Corneal Opacity ; Diagnosis ; Fabry Disease* ; Female ; Humans ; Male ; Mothers ; Sequence Deletion ; Siblings

BACKGROUND: Bioprostheses for cardiovascular surgery have limitations in their use following as calicification. alpha-galactosidase epitope is known as a stimulant of immune response and then shows a progressing calcification. The objective of this study was to evaluate histologic characteristics and mechanical properties of decellularization and treated with alpha-galactosidase. MATERIALS AND METHODS: Bovine pericardial tissues were allocated into three groups: fixation only with glutaraldehyde, decellularization with sodium dodesyl sulfate and decellularization plus treatment with alpha-galactosidase. We confirmed immunohistological characteristics and mechanical properties as fatigue test, permeability test, compliance test, tensile strength (strain) test and thermal stability test. RESULTS: Decellularization and elimination of alpha-gal were confirmed through immunohistologic findings. Decellularization had decreased mechanical properties compared to fixation only group in permeability (before fatigue test p=0.02, after fatigue test p=0.034), compliance (after fatigue test p=0.041), and tensile strength test (p=0.00). The group of decellularization plus treatment with alpha-galactosidase had less desirable mechanical properties than the group of decellularization in concerns of permeability (before fatigue test p=0.043) and strain test (p=0.001). CONCLUSION: Favorable decellularization and elimination of alpha-gal were obtained in this study through immunohistologic findings. However, those treatment including decellularization and elimination of alpha-gal implied the decreased mechanical properties in specific ways. We need more study to complete appropriate ioprosthesis with decellularization and elimination of alpha-gal including favorable mechanical properties too.
alpha-Galactosidase ; Bioprosthesis ; Compliance ; Fatigue ; Glutaral ; Pericardium ; Permeability ; Sodium ; Sprains and Strains ; Tensile Strength

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

OBJECTIVETo investigate the interaction of deficiency in thrombosis-related gene in a mouse model.

METHODSTo generate mice carrying mutations in alpha-galactosidase A (Gla) and factor V Leiden (Fvl) and analyze the phenotypes, namely, tissue fibrin deposition and thrombus formation in organs.

RESULTSFibrin deposition in organs of mice carrying both mutations in Gla and Fvl was significantly increased compared with that in mice with single mutaton: [Gla(-/0) Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=(0.28+/-0.03)% vs.(0.07+/-0.007)%, P<0.01; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=(0.28+/-0.03)% vs.(0.11+/-0.02)%, P< 0.01. Meanwhile, the number of thrombi on organ sections of mice carrying both mutations in Gla and Fvl was significantly increased compared with the single mutation carrier: [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=1.9+/-0.7 vs. 0.0+/-0.0, P<0.05; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs. [Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=1.9+/-0.7 vs. 0.3+/-0.1, P<0.05.

CONCLUSIONThese observations demonstrated that there was synergistic effect in Gla and Fvl deficiency in mice. It suggested that there could be a combination of GLA deficiency and FVL or other thrombosis-related gene defect in patients with genetic severe early-onset thrombosis.

Animals ; Factor V ; genetics ; Fibrin ; metabolism ; Immunohistochemistry ; Mice ; Mutation ; Thrombosis ; genetics ; metabolism ; alpha-Galactosidase ; genetics

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 a X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A. This abnormality in enzyme results intracellular accumulation of globotriaosylceramide and leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. We report a 35 year-old man who had been suffered from acroparesthesia aggravated by body temperature elevation and with asymptomatic renal function impairment, which were proven to be due to Fabry disease. We performed gene analysis by PCR direct sequencing and confirmed missense mutation of GLA gene. Recently enzyme replacement of alpha-galactosidase was introduced and we think that the importance of early diagnosis and treatment should be emphasized.
Adult ; alpha-Galactosidase* ; Body Temperature ; DNA Mutational Analysis ; Early Diagnosis ; Fabry Disease* ; Humans ; Mutation, Missense ; Polymerase Chain Reaction ; Proteinuria

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

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