11/262. Atypical Fabry's disease presenting with cholesterol crystal embolization.We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.- - - - - - - - - - ranking = 1keywords = disease (Clic here for more details about this article) |
12/262. angiokeratoma corporis diffusum (Anderson-Fabry's disease): a case report.We report on a 14-year-old boy who presented with a 4-year history of acral pains and febrile episodes. On physical examination, numerous small reddish papules were present on his abdomen, located predominantly on the periumbelical region. Renal function was within normal limits. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels. Histopathological examination of one of the cutaneous papules showed several dilated blood vessels in the superficial dermis surrounded by collarettes of thickened rete ridges, consistent with a diagnosis of angiokeratoma. The electron-microscopic study of a skin specimen demonstrated the presence of dilated lysosomes with deposition of electron-dense bodies, some of which with laminated structure, in endothelial cells and fibroblasts. These findings were regarded as indicative of Fabry's disease. Subsequent biochemical analysis confirmed the presence of a alpha-galactosidase A deficiency in leukocytes. In conclusion, we described the clinical, histopathological and submicroscopic findings of a case of Fabry's disease, in which the combination of electron microscopic and biochemical approaches allowed the correct diagnosis.- - - - - - - - - - ranking = 1keywords = disease (Clic here for more details about this article) |
13/262. Identification of four novel mutations in five unrelated Korean families with fabry disease.fabry disease is a X-linked recessively inherited metabolic disorder, which results from the deficient activity of the lysosomal hydrolase alpha-galactosidase A leading to the systemic deposition of glycosphingolipids with terminal alpha-galactosyl moieties. Single-strand conformation polymorphism (SSCP) analysis was performed, followed by dna sequencing of PCR amplified exons of the human alpha-galactosidase A gene in 5 unrelated Korean patients with classic fabry disease. Five different mutations were identified; two nonsense mutations (Y86X and R342X), one missense mutation (D266N), and two small deletions (296del2 and 802del4). Except for R342X mutation, four were novel mutations (Y86X, D266N, 296del2, 802del4). A T to G transversion at nucleotide position 5157 in exon 2 caused a tyrosine-to-stop substitution at codon 86. A G to A transition at position 10287 in exon 5 substituted an asparagine for an aspartate at codon 266. Mutation 296del2 in exon 2 resulted in a frame shift with a stop signal at the 22th codon downstream from the mutation, whereas mutation 802del4 resulted in a stop codon at the site of 4 bp deletion. In addition, the 802del4 was found to be a de novo mutation. This is the first report on mutation analysis of the human alpha-galactosidase A gene in Korean patients with fabry disease.- - - - - - - - - - ranking = 1.1666666666667keywords = disease (Clic here for more details about this article) |
14/262. Clinical features of and recent advances in therapy for fabry disease.fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of fabry disease. The finding of a marked decreased activity of alpha-galactosidase A in white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. Our recently completed double-blind, placebo-controlled trial of intravenous infusions of alpha-galactosidase A in patients with fabry disease demonstrated the safety and efficacy of this treatment. JAMA. 2000;284:2771-2775.- - - - - - - - - - ranking = 1.1666666666667keywords = disease (Clic here for more details about this article) |
15/262. Coexistence of Fabry's disease and necrotizing and crescentic glomerulonephritis.The coexistence of Fabry's disease, an X-linked hereditary disease, and other renal diseases, has rarely been described in the same patient. Combined Fabry's disease and pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) is hitherto unreported. We present the clinical and pathologic data of two patients with combined Fabry's disease and NCGN. Both patients presented with fevers of unknown origin and progressive renal insufficiency, however, lacked any other pathognomic signs of Fabry's disease such as acroparesthesias, dyshidrosis, and cutaneous angiokeratomas. The possible pathogenic mechanisms and causal relationship between the two disease processes are discussed.- - - - - - - - - - ranking = 1.8333333333333keywords = disease (Clic here for more details about this article) |
16/262. Histopathologic findings of cornea verticillata in a woman heterozygous for Fabry's disease.PURPOSE: To report the histopathologic findings of the cornea verticillata observed in a woman who was heterozygous for Fabry's disease. METHOD: A 67-year-old woman was found to have a whorl-like corneal opacity on her visit to the Department of ophthalmology. Aichi Saiseikai Hospital. Her visit was because of a sudden loss of vision in her right eye owing to a central retinal artery occlusion in association with an ophthalmic artery occlusion. The patient died suddenly of an acute heart failure; with family consent, an autopsy was performed and the right eye was removed for histopathologic examination by light and electron microscopy. RESULTS: Low levels of alpha-galactosidase in the leukocytes together with the corneal finding led to the diagnosis of heterozygous Fabry's disease. light microscopy revealed a 0.3- to 0.5-microm thick layer between the epithelial and Bowman's layers. Oil red O positive deposits were accumulated in the subepithelial layer, and the density varied in different regions. Electron microscopy showed that subepithelial layer differed in thickness, and the basal lamina reduplicated regionally. We were not able to determine the structure that correlated with the "ridge" in the central part of the cornea. CONCLUSION: The oil red O positive deposits and their variation in density in the subepithelial area of the cornea may have caused the characteristic whorl-like corneal opacity in this woman who was heterozygous for Fabry's disease.- - - - - - - - - - ranking = 1.1666666666667keywords = disease (Clic here for more details about this article) |
17/262. A new case of alpha-n-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation.alpha-n-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. We report a further case in a 47-year-old Japanese woman, the product of a consanguineous marriage. The remarkable findings in this patient were her normal intelligence, Meniere's syndrome, disturbance of peripheral sensory nerves, hearing loss and cardiac hypertrophy. alpha-NAGA enzyme activity in her plasma was 0.77% of the normal value. Other enzyme activities, such as alpha-galactosidase, beta-galactosidase, alpha-l-fucosidase, beta-mannosidase and aspartylglucosaminidase, were within normal limits. A large quantity of amino acid O-glycans was detected in her urine. Gene analysis revealed a novel point mutation (G-->A transition) at nucleotide 11018 (986 in the cDNA) resulting in an Arg-329-Gln substitution. Kanzaki disease has the same enzyme defect as Schindler disease, but the manifestations are quite different.- - - - - - - - - - ranking = 0.5keywords = disease (Clic here for more details about this article) |
18/262. Co-existence of lysosomal storage diseases in a consanguineous family.lysosomal storage diseases are rare and coexistence of more than one in a family can present a diagnostic challenge as illustrated by this study. The index case born to consanguineous Asian parents presented with developmental delay. Investigations led to an incidental finding of fabry disease. After numerous additional investigations over a year, a second diagnosis of aspartylglucosaminuria (AGU) was made. A family history of renal disease and developmental delay was disclosed. The sister and first cousin of the index case were diagnosed as homozygous for AGU, but do not have fabry disease. The younger brother has since been diagnosed with both fabry disease and AGU. Another cousin has learning difficulties and fits, but is heterozygous for AGU, and possibly has another uncharacterised autosomal recessive disorder. In a family with consanguinity when the clinical picture in an individual is not fully explained by the presence of one rare metabolic disease, it is essential to investigate further for the presence of others.- - - - - - - - - - ranking = 1.6666666666667keywords = disease (Clic here for more details about this article) |
19/262. ventricular fibrillation refractory to automatic internal cardiac defibrillator in Fabry's disease. review of cardiovascular manifestations.Fabry's disease is a disorder of glycosphingolipid metabolism leading to alpha-galactosidase deficiency with systemic sequelae. Clinical cardiac manifestations include dysrhythmias, structural abnormalities apparent on echocardiography, and histologic changes secondary to glycosphingolipid deposition. The introduction of automated internal cardiac defibrillators (AICD) has been shown to decrease the incidence of circulatory collapse in individuals with known terminal arrhythmias. We present a patient with Fabry's disease, who underwent coronary angiography without finding of obstructive disease. He returned after aborted sudden cardiac death necessitating the placement of an AICD. He again presented after an episode of ventricular fibrillation refractory to internal defibrillation necessitating advanced life support, and subsequently expired. We review the electrocardiographic, cardiovascular structural, and histologic manifestations of Fabry's disease.- - - - - - - - - - ranking = 1.3333333333333keywords = disease (Clic here for more details about this article) |
20/262. A missense mutation, A156T, in the alpha-galactosidase A gene causes typical fabry disease.AIMS: fabry disease is a rare but important cause of end-stage renal disease. Recent molecular investigations on alpha-galactosidase A (alpha-Gal A) have proven the existence of atypical variants in fabry disease, making genotype assessment of each phenotype indispensable. We report here a missense mutation, which causes a typical form of fabry disease. MATERIAL AND methods: The proband, a 45-year-old man, presented with acroparesthesias, hypohidrosis, left ventricular hypertrophy, renal involvement (proteinuria and renal insufficiency) with typical microscopic findings and extremely reduced plasma alpha-Gal A activity, indicating the typical form of the disease. Total rna was isolated from the proband's cultured fibroblasts, reverse-transcribed and amplified for direct sequencing of alpha-Gal A. Genomic dna of the proband's mother and 75 controls (50 males and 25 females) living in the same area as the proband was also examined. RESULTS: Sequencing of the cDNA revealed a substitution of G to A in codon 156 of alpha-Gal A, resulting in a single amino acid change from alanine to threonine (A156T). The mutation can be detected with PCR-RFLP with SfaNI digestion. This technique revealed that the mother was a heterozygote of A156T with no A156T noted in the 100 haplotypes of the controls. With a vigorous search of the same mutation in the literature, no previous description was found other than one case listed in several review papers as a classic phenotype without any other information. In our study, we examined A156T in a pedigree and demonstrated that the mutation was not a polymorphic variant in our area. CONCLUSION: Taken together, the present results strongly suggest that the missense mutation, A156T, in the alpha-Gal A gene causes typical fabry disease.- - - - - - - - - - ranking = 1.6666666666667keywords = disease (Clic here for more details about this article) |
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