Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.
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PMID:Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease. 1947 16

Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of alpha-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.
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PMID:Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease. 1970 61

Fabry's disease is an inherited lysosomal storage disorder characterized by the lack of enzyme alpha-galactosidase A (alpha-Gal A) which degrades globotriaosylceramides (Gb3) into products with lower molecular weight. The accumulation of Gb3 in different cell types is responsible for the variety of clinical manifestations. The renal function, estimated via proteinuria, hematuria and reduction of glomerular filtration rate (GRF), is heavily affected. Currently, substitution of alpha-Gal A remains the only therapeutic option for patients with Fabry's disease. Two products are approved for the treatment of Fabry's disease: agalsidase alfa and agalsidase beta. Both of these enzymes have shown a stabilization of renal function in various studies when evaluated by the creatinine clearance, estimated GFR, and serum creatinine. The pro gnosis has proven to be significantly better in cases of mild or moderate renal insufficiency from the baseline. For this reason, an early substitution of the lacking enzyme is necessary. Furthermore, enzyme replacement therapy (ERT) has proven efficient in reducing the amount of intracellular Gb3 and Gb3 in urine. Without treatment, an eGFR reduction of approximately 12 ml/min/year has been reported. After diverse studies of ERT, no significant correlation between enzyme substitution and improvement of patients' proteinuria could be shown. Furthermore, renoprotective drugs have not been consistently applied so far in the ERT trials. In any case, further studies to evaluate the long-term effect of ERT on the morbidity and mortality of patients with Fabry's disease are necessary.
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PMID:[Effect of enzyme replacement therapy (ERT) on renal function of patients with Fabry's disease]. 1977 74

We present a 22-year-old male patient who showed both classical Fabry disease and IgA nephropathy. He had proteinuria (1.5 g/day), hypohidrosis and neuralgia with fever. Serum creatinine and blood urea nitrogen were 0.9 mg/dL and 11.4 mg/dL, respectively. Renal biopsy showed strikingly vacuolated podocytes and tubular epithelium cells. Myelin-like bodies were detected in podocytes, mesangial cells, endothelial cells and tubular epithelium cells by electron microscopy. On immunofluorescence microscopy, IgA and C3 deposits were detected in mesangial areas. From these results and a markedly low level of alpha-galactosidase A activity, this patient was diagnosed as having classical Fabry disease and IgA nephropathy.
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PMID:Hemizygous Fabry disease associated with IgA nephropathy: a case report. 1981 2

Fabry disease is a progressive and life-threatening glycolipid storage disorder affecting both males and females. The primary driver of the disease is the accumulation of glycolipids (globotriaosylceramide [GL-3]) in a variety of cell types, including vascular endothelial cells, a range of renal cell types, cardiomyocytes and neurons, which is caused by deficient activity of the lysosomal enzyme, alpha-galactosidase. The disease typically presents during childhood or adolescence. First manifestations reflect involvement of small nerve fibres of the peripheral and autonomic nervous systems. With age, severe complications involving the kidneys, heart and brain cause considerable morbidity and premature death. Outside the US, enzyme replacement therapy (ERT) with agalsidase alfa 0.2 mg/kg every other week (EOW) and agalsidase beta 1.0 mg/kg EOW is available for the treatment of patients with Fabry disease, while agalsidase beta 1.0 mg/kg EOW is the only approved drug in the US. To analyse the evidence for ERT, a systematic review of the literature was performed to identify prospectively designed randomized, controlled trials (RCTs) and open-label studies on the efficacy of agalsidase alfa and agalsidase beta. MEDLINE and EMBASE databases were searched; inclusion criteria for the systematic review were prospectively designed clinical studies evaluating ERT with quantifiable endpoints: double-blind and open-label studies were eligible. Exclusion criteria were review articles, case reports, case studies, letters to the editor and articles based on registry data (Fabry Outcome Survey or Fabry Registry). In addition, any studies with a retrospective design or data based on post hoc analyses were excluded. The evidence was reviewed with respect to the clinical benefits of ERT at the level of the end organ. A total of 9 RCTs and 23 open-label studies were identified for inclusion. The efficacy of ERT in Fabry disease has been measured against a variety of endpoints, the majority of which were subclinical parameters rather than clinical outcomes. Plasma levels of GL-3 together with accumulation in the kidney, heart and skin were the most commonly studied endpoints, followed by renal endpoints of proteinuria and glomerular filtration rate, whereas cardiac and neurological endpoints were not commonly studied. To date, only one RCT with ERT defined hard clinical outcomes in the form of cardiac, renal or cerebrovascular events, or death as its primary endpoint. The currently available data from prospective RCTs and open-label studies in patients with Fabry disease are more robust for ERT at a dose of 1 mg/kg EOW than a dose of 0.2 mg/kg EOW, although the beneficial effects of ERT with either dose or preparation are variable.
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PMID:Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. 1985 24

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in alpha-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease.
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PMID:A case of minimal change disease in a Fabry patient. 1987 52

Fabry disease is an X-linked recessive glycolipid storage disease. It is caused by deficiency of the lysosomal enzyme alpha-galactosidase A and leads to the accumulation of the enzyme substrate, globotriasylceramide (Gb3) in many tissues including endothelial cells, pericytes and smooth muscle cells of blood vessels, renal epithelial cells, cardiac myocytes and numerous neuronal cells. In this report, we present 20-year-old male patient with ischemic stroke in pons. The case had previously been misdiagnosed as polimyositis and vasculitis. Angiokeratomas, neuropathic pain and ischemic stroke in young age suggested a Fabry disease. The diagnosis was confirmed biochemically and genetically. All young adults with stroke, especially if they have additional symptoms like angiokeratomas, proteinuria, neuropathic pain in toes and fingers should be tested for Fabry disease.
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PMID:Neurological manifestation of Fabry disease--a case report. 2012 Apr 9

We describe the case of a 27-year-old woman with a family history of Anderson-Fabry disease (AFD). Urinary sediment presented microhematuria and 0.9 g/24 hours proteinuria. The alpha-galactosidase A measurement in fibroblasts showed partial deficit of the enzyme, which was compatible with being a carrier of the illness. Renal biopsy gave evidence of kidney lesions from Fabry disease. Genetic study revealed mutation C52Y or Cys52Tyr, which has not been previously described and had also been detected in the father of the patient. During follow-up, the presence of hypergammaglobulinemia revealed an underlying HIV disease. She is now awaiting enzymatic substitution treatment.
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PMID:New mutation in female patient with renal variant of Fabry disease and HIV. 2015 22

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by the deficient activity of alpha-galactosidase A which results in the accumulation of neutral glycosphingolipids in various tissues leading particularly to vasculopathy, cardiomyopathy, neuropathy, and chronic kidney disease. It results in substantial morbidity and premature death in affected patients. Although there are some signs and symptoms suggestive of FD including painful crisis, angiokeratomas, and corneal changes, the majority of FD complications are non-specific (left ventricular hypertrophy, conduction abnormalities, vascular spasms, proteinuria, renal insufficiency), which is why FD still remains largely underdiagnosed. The mechanism by which accumulating glycosphingolipids cause multiorgan disorder is not yet completely understood as it cannot be explained by pure substrate storage. Besides standard therapy of different medical problems in FD patients, specific enzyme replacement therapy has been introduced in the last few years.
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PMID:Fabry disease - Vascular manifestations. 2046 67

Fabry disease is caused by an alpha-galactosidase A (GLA) deficiency. In this study, we identified 28 unrelated Korean families with Fabry disease with 25 distinct mutations in the GLA gene including six novel mutations (p.W47X, p.C90X, p.D61EfsX32, IVS4(-11)T>A, p.D322E and p.W349). Notably, five subjects from four unrelated families carried the p.E66Q variant, previously known as a pathogenic mutation in atypical Fabry disease. Among these patients, only one had proteinuria and two had hypertrophic cardiomyopathy without any other systemic manifestation of Fabry disease. Substantial residual GLA activity was shown both in the leukocytes of p.E66Q patients (19.0-30.3% of normal activity) and in transiently overexpressed COS-7 cells (43.8 + or - 3.03% of normal activity). Although GLA harboring p.E66Q is unstable at neutral pH, the enzyme is efficiently expressed in the lysosomes of COS-7 cells. The location of p.E66 is distant from both the active site and the dimer interface, and has a more accessible surface area than have other mutations of atypical Fabry disease. In addition, the allele frequency of p.E66Q determined in 833 unrelated Korean individuals was remarkably high at 1.046% (95% confidence interval, 0.458-1.634%). These results indicate that p.E66Q is a functional polymorphism rather than a pathogenic mutation.
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PMID:Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns. 2050 83


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