Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anderson-Fabry disease (AFD) is a lysosomal storage disorder (LSD) due to alpha-galactosidase A (alpha-Gal A) deficiency and the resultant accumulation of incompletely metabolised glycosphingolipids (GSLs), primarily globotriosylceramide (Gb(3)), within various tissues. It is an X-linked multisystem disorder characterised by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement, and associated with significant impact on quality of life and diminished lifespan. The disease manifests primarily in hemizygous males; however, there is increasing recognition that heterozygous (carrier) females may also develop disease-related complications, although onset among affected women may be delayed. Until recently, treatment has been limited to symptomatic management of pain and other measures to alleviate the problems associated with end-stage complications from renal, cardiac and nervous system involvement. The availability of the recombinant enzyme offers the potential of a safe and effective targeted treatment approach. At the moment, two distinct enzyme formulations are approved in Europe (and in other countries) and both continue to undergo FDA evaluation in the US. Increasing knowledge of the natural history of AFD and greater experience with enzyme therapy should enable optimal patient care. The relative rarity and complexity of AFD necessitates a multi-disciplinary team approach that may be facilitated by a centralised registry.
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PMID:Advances in the management of Anderson-Fabry disease: enzyme replacement therapy. 1189 Aug 71

Anderson-Fabry disease (AFd) is caused by an X-linked inborn error in the glycosphingoLipid metabolic pathway due to an enzymatic defect in a lysosomal hydrolase: alpha-galactosidase A. The defect results in the progressive accumulation of neutral glycosphingolipids in most body fluids and several tissues. The clinical manifestations of AFd are related to organ damage and, obviously, are more severe in hemizygous males than in heterozygous females. In the third decade of life, the course of the disease involves severe deterioration of kidney function progressing to end-stage renal failure. All kind of cells of renal structures are filled with glycosphingolipid deposits. Electron microscopic studies document typical intracytoplasmic osmiophilic bodies with a characteristic "zebra" or "onion-skin" appearance due to concentric lamellation of alternating clear and dark layers. Clinical interest in Fabry patients is related to recent advances in treatment with an intravenous specific enzyme to modify the biochemical error of the glycosphingolipid catabolic pathway.
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PMID:Renal ultrastructural findings in Anderson-Fabry disease. 1201 25

Anderson Fabry Disease (AFD) is an extremely painful and debilitating multi-system X-linked disorder due to alpha-galactosidase enzyme deficiency. To date, no baseline data on health-related quality-of-life (HR-QoL) have been reported in males affected with this condition. In this study, 38 males with AFD completed Medical Outcomes Study Short Form, EuroQoL questionnaires and an AFD-specific questionnaire prior to the start of a trial involving replacement therapy with alpha-galactosidase. Results from these questionnaires were compared to the results from a similar HR-QoL study in males with severe haemophilia (factor VIII/IX deficiency) that used the same questionnaires and to the results of two large normative studies. The results on both questionnaires showed that in most instances males with AFD recorded significantly lower HR-QoL compared with males in the general population and individuals with severe haemophilia after adjusting for differences in age. These findings suggest therefore, that the scope for improvement in HR-QoL as a result of treatment with an appropriate agent is extremely large.
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PMID:Assessment of health-related quality-of-life in males with Anderson Fabry Disease before therapeutic intervention. 1201 36

Anderson-Fabry disease is an X-linked multisystemic disorder caused by a genetic deficiency of the lysosomal enzyme a-galactosidase A. The enzyme is responsible for degradation of glycolipids inside the lysosomes. Lack of catalytic activity leads to progressive depositions of undegraded glycolipids in a large number of organs. Crises of severe pain in the extremities (acroparesthesias), hypohidrosis, corneal opacities and dysfunction of several organs (kidney, brain, heart) are the leading symptoms in patients with Anderson-Fabry disease. Females may have the same symptoms as males but to a more variable degree. The variable manifestations seen in heterozygotes can be explained by the Lyon hypothesis. This hypothesis predicts that in X-linked diseases, the carriers are a mosaic of normal and mutant cells in varying proportions and hence have variable expression. As in Gaucher's disease, enzyme replacement therapy recently became available for Anderson-Fabry disease. Two drugs have gained approval in the EU by the European Agency for the Evaluation of Medicinal Products. These are agalsidase beta (Fabrazyme, Genzyme Corporation) and agalsidase alfa (Replagal, Transkaryotic Therapies, Inc.). This review will describe clinical efficacy, safety and tolerability of agalsidase alfa.
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PMID:Agalsidase alfa--a preparation for enzyme replacement therapy in Anderson-Fabry disease. 1203 28

Anderson-Fabry disease (AFd) is a rare X-linked disorder characterized by deficiency of alpha-galactosidase A that leads to systemic accumulation of neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), in body fluids and visceral tissues, including the kidney. End-stage renal failure is a common manifestation in hemizygous males that often occurs by the third to fourth decade of life. Usually transplanted patients exhibit improvement in clinical symptoms of the disease, probably related to the production of alpha-galactosidase A from the grafted kidney, but mainly related to the increase in Gb3 clearance by the functioning kidney, and increased survival of red cells due to the correction of the uremic status with an evident decrease in the production of Gb3 depending from hemolysis. Several Fabry patients with successful kidney graft survived for 10-15 years and died for cardiovascular complications related to the metabolic disease. The loss of grafted kidney is due to rejection, thrombosis or sepsis. An important issue considering renal transplantation in AFd is the recurrence of the disease in the kidney graft; however, no evidence regarding this possibility has occurred up to now. We report herein the ultrastructural study of the urinary sediment of a 35-year-old male Fabry patient with a severe clinical form of the disease with progression to ESRF at age 29, and submitted to renal transplantation at 33 years. Ultrastructural findings of the urinary sediment documented several cells, probably tubular epithelial cells, with typical accumulation of myelinic bodies resulting from intracellular storage of neutral glycosphingolipids. This morphological evidence arises the problem of the possible recurrence of AFd in the kidney graft in patients with severe phenotype of the metabolic disease.
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PMID:Renal transplantation in patients with Fabry disease. 1205 80

Fabry's disease is a lipid storage disease caused by an X-linked hereditary deficiency of alpha-galactosidase. The enzymatic defect causes progressive deposition of ceramide trihexoside (CTH) in various tissues, leading to renal failure, premature myocardial infarction, and stroke, with a high rate of mortality in younger patients. Among the complications associated with Fabry's disease, a few cases involving avascular necrosis (AVN) of the femoral head have been reported. However, direct evidence of deposition of CTH in bone marrow in the femoral head has not been demonstrated. This report describes a 58-year-old man who underwent total hip arthroplasty for femoral head AVN associated with Fabry's disease. The accumulation of CTH was examined by chemical analysis of the sphingolipid extracted from the femoral head, using delayed-extraction matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. This is the first report confirming the presence of CTH in the sphingolipid fraction from normal and necrotic bone of a patient with Fabry's disease.
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PMID:Avascular necrosis of the femoral head in a patient with Fabry's disease: identification of ceramide trihexoside in the bone by delayed-extraction matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. 1212 77

Anderson-Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriasylceramide throughout diverse cells, tissues and organs of the body. The disease usually presents in childhood, is progressive, and results in increasing disability and premature death. Female carriers tend to be less severely affected. AFD is difficult to diagnose because of its heterogeneous signs and symptoms. Awareness is low among health professionals, and diagnosis is typically delayed for several years after first presentation. Treatment was formerly entirely symptomatic, but enzyme replacement therapy has recently been licensed and management is evolving from genetic counselling and palliative care to early diagnosis and active intervention.
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PMID:New developments in the management of Anderson-Fabry disease. 1232 36

Fabry disease (FD, OMIM 301500) is an X-linked inherited disorder of metabolism due to mutations in the gene encoding alpha-galactosidase A, a lysosomal enzyme. The enzymatic defect leads to the accumulation of neutral glycosphingolipids throughout the body, particularly within endothelial cells. Resulting narrowing and tortuosity of small blood vessels lead to tissue ischaemia and infarction. Inability to prevent the progression of glycosphingolipid deposition causes significant morbidity (acroparesthesia, angiokeratoma, autonomic dysfunction, cardiomyopathy and deafness), and mortality from early onset strokes, heart attack and renal failure in adulthood. Demonstration of alpha-galactosidase A deficiency in leukocytes or plasma is the definitive method for the diagnosis of affected hemizygous males. Most heterozygotes present with a cardiac, renal or neurological symptomatology, although to a lesser extent than what is observed in hemizygotes. Due to random X-chromosomal inactivation, enzymatic detection of carriers is often inconclusive. Molecular testing of possible carriers is therefore mandatory for accurate genetic counselling. The GLA gene has been cloned and more than 200 mutations have been identified. Medical management is symptomatic and consists of partial pain relief with analgesic drugs (gabapentin, carbamazepine), whereas renal transplantation or dialysis is available for patients experiencing end-stage renal failure. However, the ability to produce high doses of alpha-galactosidase A in vitro has opened the way to clinical studies and enzyme replacement therapy has recently been validated as a therapeutic agent for FD patients in clinical trials. Long term safety and efficacy of replacement therapy are currently being investigated.
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PMID:[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]. 1236 Jul 45

Fabry disease (FD, OMIM 301500) is an X-linked inherited disorder of metabolism due to mutations in the gene encoding alpha-galactosidase A, a lysosomal enzyme. The enzymatic defect leads to the accumulation of neutral glycosphingolipids throughout the body, particularly within endothelial cells. Resulting narrowing and tortuosity of small blood vessels with endothelial dysfunction lead to tissue ischaemia and infarction. Inability to prevent the progression of glycosphingolipid deposition causes significant morbidity and mortality from early onset strokes, cardiomyopathy and renal failure in adulthood. Medical management is symptomatic and consists of partial pain relief with analgesic drugs (gabapentin, carbamazepine), antihypertensive drugs, whereas renal transplantation or dialysis is available for patients experiencing end-stage renal failure. However, the ability to produce high doses of alpha-galactosidase A in vitro has opened the way to preclinical studies in the mouse model, and to the development of the first clinical trials in patients with Fabry disease. Enzyme replacement therapy has recently been validated as a therapeutic agent for Fabry disease patients. Long term safety and efficacy of replacement therapy are currently being investigated. Substrate deprivation and gene therapy may also prove future alternative therapeutic options.
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PMID:[Fabry's disease (alpha-galactosidase-A deficiency): recent therapeutic innovations]. 1236 Jul 47

Fabry disease is an X-linked inherited disorder of metabolism due to mutations in the gene encoding alpha-galactosidase A, a lysosomal enzyme. The enzymatic defect leads to the systemic accumulation of incompletely metabolised glycosphingolipids, primarily globotriaosylceramide, in plasma and lysosomes within various tissues. Inability to prevent the progression of glycosphingolipid deposition causes significant morbidity, associated with significant impact on quality of life and diminished lifespan from early onset strokes, heart attack and progressive renal failure. The disease manifests primarily in hemizygous males; however, there is increasing recognition that heterozygous (carrier) females may also develop disease-related complications. Indeed, most heterozygotes present with cardiac, renal or neurological symptoms, although with later-onset and to a lesser extent than is observed in hemizygotes. Until recently, medical management was symptomatic, consisting of partial pain relief with analgesic drugs (carbamazepin, gabapentin), kidney and vascular protection with angiotensin-converting enzyme inhibitors, statins and folic acid, whereas renal transplantation or dialysis is available for patients experiencing end stage renal failure. The ability to produce high doses of alpha-galactosidase A has opened the way to preclinical studies, and enzyme replacement therapy has recently been validated as a therapeutic agent in clinical trials. Long-term safety and efficacy of replacement therapy are currently being investigated. Increasing knowledge of the natural history of Fabry disease and greater experience with enzyme therapy should enable optimal patient care. The complexity and relative rarity of Fabry disease necessitates a multi-disciplinary team approach that may be facilitated by a disease registry.
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PMID:Fabry disease: recent advances in enzyme replacement therapy. 1238 6


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