1/29. Induced sputum examination: diagnosis of pulmonary involvement in Fabry's disease.Fabry's disease is a rare inherited metabolic disorder caused by a deficiency in the enzyme alpha-galactosidase A. It can affect almost every organ, including the lungs. Confirmation of lung involvement has depended on invasive bronchial biopsy specimens or brushings to confirm the presence of typical lamellar inclusion bodies within bronchial epithelial cells. We report a patient with known Fabry's disease in whom these inclusion bodies were identified by examination of induced sputum.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
2/29. 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 = 1keywords = metabolic disorder (Clic here for more details about this article) |
3/29. Clinical features and genetic analysis of a Chinese kindred with Fabry's disease.BACKGROUND: Fabry's disease is an X-linked recessive inborn error of glycosphingolipid catabolism resulting from deficient activity of lysosomal enzyme alpha-galactosidase A causing occlusive microvascular diseases affecting the kidney, heart, peripheral nerves and brain. It is an uncommon disease in the Oriental population. methods AND RESULTS: We report a Chinese kindred of Fabry's disease and the relevant clinical features are discussed. The diagnosis of Fabry's disease was based on serum alpha-galactosidase A activity and typical histological features from renal biopsy in the index patient. Genetic analysis of two hemizygous male patients revealed a missense mutation predicting a leucine to proline substitution (L14P) in the alpha-galactosidase gene causing classical Fabry's disease in this family. This is a novel point mutation not described previously in the literature and the second report describing novel genetic mutations for Fabry's disease in Chinese patients. CONCLUSIONS: Fabry's disease is rare in Chinese patients but this diagnosis should be considered in patients with positive family history of kidney disease and relevant clinical features.- - - - - - - - - - ranking = 0.00051469603724097keywords = brain (Clic here for more details about this article) |
4/29. fabry disease: immunocytochemical characterization of neuronal involvement.fabry disease is an X-linked glycosphingolipid storage disease caused by deficiency of alpha-galactosidase. Storage of globotriaosylceramide, also known as ceramide trihexoside, is maximal in blood vessels but also occurs in neurons. We performed neuropathological histochemical studies on the brains and spinal cords of 2 patients with confirmed fabry disease. Luxol fast blue-positive deposits were found in blood vessels throughout the central and peripheral nervous system and within selected neurons in spinal cord and ganglia, brainstem, amygdala, hypothalamus, and entorhinal cortex. Regions adjacent to involved neuronal groups, including nucleus basalis, striatum, globus pallidus, and thalamus, were spared. Electron microscopy showed lamellar cytoplasmic neuronal inclusion bodies. Using a monoclonal antibody reactive with ceramide trihexoside, we found more extensive neuronal deposition than evident by Luxol-fast blue staining and new areas of neuronal storage in the spinal cord and cerebral cortex. blood vessels throughout the nervous system were strongly immunoreactive. The highly selective pattern of neuronal involvement we found suggests that glycosphingolipid exposure, uptake, or catabolism varies greatly with respect to neuronal morphology and distribution. The degree of toxicity to neurons and the clinical significance of this neuronal storage remains to be defined.- - - - - - - - - - ranking = 0.0093195456781562keywords = nervous system, brain (Clic here for more details about this article) |
5/29. neurologic manifestations of Kanzaki disease.We describe the neurologic findings in a patient with alpha-n-acetylgalactosaminidase deficiency (Kanzaki disease). Clinical and electrophysiologic studies revealed sensory-motor polyneuropathy, and sural nerve pathology showed decreased density of myelinated fibers with axonal degeneration. The patient had mildly impaired intellectual function with abnormal brain MRI and sensory-neuronal hearing impairment with repeated episodes of vertigo attacks. These findings suggest that Kanzaki disease may develop neurologic complications in the CNS and peripheral nervous system.- - - - - - - - - - ranking = 0.0046597728390781keywords = nervous system, brain (Clic here for more details about this article) |
6/29. Effect of enzyme-replacement therapy on gastrointestinal symptoms in fabry disease.fabry disease is an X-linked recessive lysosomal storage disorder caused by deficiency of lysosomal alpha-galactosidase A. The disease affects not only kidney, myocardium, central nervous system and the skin but also, in many patients, the gastrointestinal tract. The recent advent of enzyme-replacement therapy has been reported to show beneficial effects on cardiomyopathy, renal function and autonomous nervous function. We report on a 34-year-old patient with fabry disease in whom gastrointestinal symptoms were major complaints. Enzyme replacements led to remarkable improvement of diarrhoea and constipation. abdominal pain, the feeling of fullness and meteorism improved, and metoclopramide, which previously had been used regularly, could be discontinued. There were also marked improvements of appetite, body weight, body mass index, physical activity and overall wellbeing. This observation should prompt further investigations into the pathophysiology of gastrointestinal manifestations in fabry disease and the mechanisms of enzyme-replacement effects on gut function.- - - - - - - - - - ranking = 0.0065690144472021keywords = nervous system, central nervous system (Clic here for more details about this article) |
7/29. Cerebrovascular manifestations in a female carrier of Fabry's disease.A female carrier of Fabry's disease with neurological manifestations is presented. An elective ophthalmological examination revealed a whorl keratopathy suggesting that the patient may be a carrier of Fabry's disease. She subsequently suffered two brainstem ischemic events. Cranial MRI examination performed revealed evidence of multiple subcortical strokes and diffuse white matter disease in her frontal lobes. Biochemical analysis confirmed that this patient was a carrier of Fabry's disease. The cerebrovascular manifestations may be secondary to tissue variability of mutant enzyme activity.- - - - - - - - - - ranking = 0.00051469603724097keywords = brain (Clic here for more details about this article) |
8/29. chloroquine-induced lipidosis mimicking fabry disease.Intracellular accumulation of phospholipids may be a consequence of inherited or acquired metabolic disorders. In fabry disease, deficiency of alpha-galactosidase A results in storage of globotriasylceramide in numerous cells including endothelium, striated muscle (skeletal, cardiac), smooth muscle, and renal epithelium among others; the ultrastructural appearance of the inclusions is of whorled layers of alternating dense and pale material ('zebra bodies' or myeline figures). chloroquine therapy may result in storage of biochemically and ultrastructurally similar inclusions in many of the same cells as fabry disease and often results in similar clinical manifestations. We report a 56-year-old woman with rheumatoid arthritis treated with chloroquine, who developed muscle weakness and renal insufficiency; information regarding therapy was not emphasized at the time of renal biopsy, leading to initial erroneous interpretation of fabry disease. Following muscle biopsy, genetic and enzyme evaluation, and additional studies on the kidney biopsy, a diagnosis of chloroquine toxicity was established. One year following cessation of chloroquine, renal and muscle dysfunction greatly improved. In chloroquine toxicity, inclusions in glomeruli are not only in visceral epithelial, endothelial and mesangial cells but are in infiltrating monocytes/macrophages, which are most commonly present in the mesangium. Curvilinear bodies, the ultrastructural features of chloroquine toxicity in striated muscle, are not present in renal cells. This report documents differences in appearance, cells affected and morphological differential diagnostic features to distinguish these two entities.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
9/29. Renal variant of Anderson-fabry disease and bilateral renal cell carcinoma.Anderson-fabry disease (AFd) is an X-linked metabolic disease with clinical manifestations secondary to accumulation of glycosphingolipids in various tissues. We report the first case in which a patient with renal variant of AFd and chronic renal failure developed bilateral conventional renal cell carcinoma. His metabolic disorder was diagnosed only after histopathologic study of the kidney specimen resected because of the tumoral lesion. There is no clear etiologic relation between the metabolic and neoplastic disease. As AFd is not common or well known and its clinical manifestations tend to be nonspecific, the disorder is often unrecognized, misdiagnosed, or diagnosed late in life. The pathologist should be aware of this disorder when evaluating a kidney specimen from patients with chronic renal failure of unknown cause.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
10/29. Bilateral femoral head and distal tibial osteonecrosis in a patient with fabry disease.fabry disease is a lysosomal storage disease caused by alpha-galactosidase A deficiency. The classic presentation of fabry disease involves multiple organs, including kidneys, heart, skin, eyes, and nervous system. osteonecrosis is rarely reported in patients with fabry disease. In this article, we describe the case of a 37-year-old white man who had fabry disease and no risk factors for osteonecrosis but who developed osteonecrosis in both femoral heads and in an unusual site, bilateral distal tibiae. Results of mutation analysis showed a nonsense mutation (R227X) in the alpha-galactosidase A gene. This case suggests that fabry disease may be a risk factor for development of osteonecrosis. The enzyme replacement therapy currently available may be an effective method of preventing this complication.- - - - - - - - - - ranking = 0.0041450768018371keywords = nervous system (Clic here for more details about this article) |
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