1/32. Different phenotypic expression in relatives with fabry disease caused by a W226X mutation.Two male relatives with fabry disease presented striking differences in clinical symptoms and age of onset. The propositus had retarded statural growth and skeletal dysplasia while his nephew suffered mainly from aggravating acroparesthesia and celiac disease. fabry disease is an X-linked inborn error of glycosphingolipid metabolism resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal A) enzyme. The alpha-Gal A gene is located at Xq22.1. Efforts to establish genotype-phenotype correlations have been limited because most patients have private mutations. In previous clinical studies performed in families with fabry disease, marked differences in phenotype are described between affected relatives. This family also demonstrates the difficulty in predicting the clinical phenotype in patients and relatives with the same alpha-Gal A mutation. Furthermore, in the absence of a family history, the diagnosis may be easily missed.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
2/32. biopsy-proven cardiomyopathy in heterozygous Fabry's disease.A 23-year-old woman with heterozygous Fabry's disease who had acroparesthesia was admitted to hospital for precise examination of the disease before childbearing. She had no cardiac-related symptoms and no abnormality on physical examination. The alpha-galactosidase A activity in her leukocytes was present, but lower than normal. However, the endomyocardial biopsy showed specific changes for Fabry's disease. As Fabry's disease is a rare X-linked recessive inborn error of glycosphingolipid metabolism, heterozygous females are usually asymptomatic, but rarely can be affected as severely as hemizygous males. This is an isolated case of heterozygous Fabry's disease in a female in whom cardiac involvement was detected by endomyocardial biopsy, although she had no cardiac abnormality on physiological examinations. In conclusion, endomyocardial biopsy is useful for evaluation of the cardiac involvement of Fabry's disease even in an asymptomatic case.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
3/32. 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 = 0.028734062580086keywords = metabolism (Clic here for more details about this article) |
4/32. Co-occurrence and contribution of fabry disease and klippel-trenaunay-weber syndrome to a patient with atypical skin lesions.fabry disease (FD) is an X-linked recessive inborn error of glycosphingolipid metabolism. Among clinical symptoms, maculopapular skin lesions, known as angiokeratoma, most often appear on the lower abdomen, scrotum, and thighs, with a tendency toward bilateral symmetry. A 30-year-old male patient was referred to us for evaluation of a complex vascular and cutaneous malformation. skin examination showed numerous angiokeratoma, which had developed only on the right part of the body, with a sharp delineation in the midline of the trunk. The diagnosis of FD was confirmed by demonstration of a decreased alpha-galactosidase A activity, and the patient was shown to be hemizygote for a missense mutation (R342Q) in the alpha-galactosidase A gene (GLA). This mutation was also demonstrated in dna extracted from fibroblast cultures established from both affected and unaffected skin areas, thus excluding the hypothesis of somatic mosaicism or revertant mosaicism. Interestingly, the diagnosis of klippel-trenaunay-weber syndrome (KTWS) was also made, through clinical and radiological investigations. This is the first report on the association between FD and KTWS. karyotype analysis was normal. It is likely that the mixed vascular malformations of KTWS affecting capillary and venous systems have contributed to the unusual angiokeratoma distribution pattern observed in the patient.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
5/32. Neurological presentation of Fabry's disease in a 52 year old man.Fabry's disease is an X linked inborn error of metabolism due to deficient activity of the lysosomal enzyme alpha galactosidase A. Previously unrecognised Fabry's disease presenting in a 52 year old man being investigated for progressive dysarthria and ataxia is discussed. brain magnetic resonance imaging suggested the presence of small vessel disease but skin biopsy (done to exclude cerebral autosomal dominant arteriopathy with subcortical infarcts and leucencephalopathy) showed typical changes of Fabry's disease. This diagnosis was confirmed by subsequent enzyme assays. The authors contend that Fabry's disease should be excluded, at least on clinical grounds, in patients with otherwise unexplained cerebrovascular disease.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
6/32. 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 = 0.97126593741991keywords = inborn error, error (Clic here for more details about this article) |
7/32. Renal involvement in Anderson-fabry disease.Anderson-fabry disease (AFd) is a rare X-linked lisosomal storage disorder of glycosphingolipid (GL) metabolism, caused by a deficiency of the activity of alpha-galactosidase A (alpha-gal A). The progressive accumulation of GL in tissues results in the clinical manifestations of the disease, that are more evident in hemizygous males, and include characteristic skin lesions (angiokeratomas), neurological symptoms (acroparesthesia), ocular features (cornea verticillata), cardiac involvement (left ventricular enlargement, conduction abnormalities), cerebrovascular manifestations (thromboses, hemorrhage, etc.), and kidney involvement with progression to end-stage renal failure (ESRF). ESRF is a common manifestation in hemizygous males (3rd-5th decade) and death occurs around the 5th decade of life because of severe cardiac and/or cerebrovascular complications. Heterozygous females have an attenuated form of this systemic disease. In the kidney, accumulation of GL occurs in the endothelial cells of every vessel, in the epithelial cells of every tubular segment, and in all kinds of glomerular cells. The broad spectrum of renal lesions is a pathophysiological continuum with progressive impairment in the renal function related to continuous intracellular deposition of GL. Electron microscopic study of renal biopsies shows typical osmiophilic inclusion bodies in the cytoplasm of all kind of renal cells, characterized by concentric lamellation of clear and dark layers (35-50 A of periodicity). ESRF is treated by dialysis and kidney transplantation: neither treatment modifies the progression of the cardiovascular and cerebrovascular lesions due to progressive GL deposition. The outcome of kidney transplantation seems to be similar to that found in other non-diabetic patients, but the survival rate on dialysis is lower than in patients with other causes of ESRF. Nowadays, treatment with enzyme replacement infusion with purified alpha-Gal A, produced by a genetically engineered human cell line or Chinese hamster ovocytes, seems to be effective and safe.- - - - - - - - - - ranking = 0.028734062580086keywords = metabolism (Clic here for more details about this article) |
8/32. Anderson-fabry disease in austria.fabry disease is an X-linked inherited inborn error of glycosphingolipid catabolism. The deficiency of alpha-galactosidase A leads to the deposition of glycosphingolipids primarily in lysosomes of blood vessel cells. In classically affected hemizygotes clinical manifestations include pain in the extremities, vessel ectasia (angiokeratoma) in skin and mucous membranes, ophthalmological abnormalities, and hypohidrosis. As disease progresses there is renal, cardiac, cerebral and vascular involvement, with most patients experiencing renal insufficiency, cardiac hypertrophy or stroke. Many female carriers of fabry disease also have symptoms. Recently available enzyme replacement therapy has the potential to control or even reverse disease progression. The present analysis reports on five Austrian families with fabry disease, cared for by nephrologists in June 2002. Furthermore we discuss potential indications for enzyme replacement therapy in patients maintained on renal replacement therapy.- - - - - - - - - - ranking = 0.97126593741991keywords = inborn error, error (Clic here for more details about this article) |
9/32. fabry disease: novel alpha-galactosidase A 3'-terminal mutations result in multiple transcripts due to aberrant 3'-end formation.Mutations in the gene that encodes the lysosomal exoglycohydrolase, alpha-galactosidase A (alpha-GalA), cause fabry disease, an X-linked recessive inborn error of glycosphingolipid catabolism. Human alpha-GalA is one of the rare mammalian genes that has its polyadenylation signal in the coding sequence and lacks a 3' untranslated region (UTR). We identified two novel frameshift mutations, 1277delAA (del2) and 1284delACTT (del4), in unrelated men with classical fabry disease. Both mutations occurred in the 3' terminus of the coding region and obliterated the termination codon, and del2 also altered the polyadenylation signal. To characterize these mutations, 3' rapid amplification of cDNA ends (RACE) and polymerase chain reactions (PCR) were performed, and the amplicons were subcloned and sequenced. Both mutations generated multiple transcripts with various lengths of 3' terminal sequences, some elongating approximately 1 kb. Mutant transcripts were classified as follows: type I transcripts had terminal in-frame thymidines that created termination codons when polyadenylated, type II had downstream termination codons within the elongated alpha-GalA sequence, and type III, the most abundant, lacked termination codons at their 3' ends. To determine if the type III transcripts were degraded by the recently described cytosolic messenger rna degradation pathway for messages lacking termination codons, northern blot analysis was performed. However, the finding of similar levels of nuclear and cytoplasmic alpha-GalA mRNA in normal and patient lymphoblasts suggested that mRNA degradation did not result from either mutation. Expression of representative transcript types revealed differences in intracellular localization and/or protein stability and catalytic activity, with most mutant proteins being nonfunctional. Characterization of these 3' mutations identified a novel molecular mechanism causing classical fabry disease.- - - - - - - - - - ranking = 0.97126593741991keywords = inborn error, error (Clic here for more details about this article) |
10/32. An unusual cause of dyspnea.The case of a 71-year-old woman who presented with dyspnea and palpitations is presented. Workup yielded a diagnosis of Fabry's disease, and the patient was referred for therapy. Fabry's disease is a disorder of glycosphingolipid metabolism and has forms that are limited to the myocardium. There is evidence that it has been underrecognized as a cause of cardiac hypertrophy. Because screening can be done with a simple blood test and new treatment options appear promising, we recommend consideration of Fabry's disease in the workup of patients with cardiac hypertrophy.- - - - - - - - - - ranking = 0.028734062580086keywords = metabolism (Clic here for more details about this article) |
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