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)

Fabry disease is a hereditary metabolic disease, with an X-linked transmission, that is due to the deficit of alpha-galactosidase A, a lysosomal enzyme. The enzyme deficiency is responsible for an accumulation of neutral glycosphingolipids in the organism with a consequent disease of overload that is responsible for pain, dermatological, renal, cardiac, gastro-intestinal, cochlear and neurological manifestations. Fabry disease starts during childhood but the diagnosis is often made too late. An early diagnosis is nevertheless essential in order to commence a treatment before the occurrence of morbid cardio or cerebro-vascular accidents, or the development of end-stage chronic renal failure. Some phenotypic variants of Fabry disease are probably under-diagnosed among patients with so-called idiopathic hypertrophic cardiomyopathy on haemodialysis. Treatment by substitution of the enzyme with a recombinant alpha-galactosidase has been recently validated in breakthrough controlled clinical trials. Substitutive enzyme treatment represents a major therapeutic development. At the same time, it raises numerous questions such as the ideal age for initiation of treatment, the dose and the optimal frequency of enzyme administration, the reversibility of certain histopathological lesions and the determination of the best markers for the assessment and follow-up of the efficacy of treatment. Monitoring of the plasma levels of the enzyme substrate and the antibody titre seem to be essential. The documentation of short-term clinical benefits could require the use of sophisticated investigation methods such as the study of the myocardial function by tissue Doppler imaging.
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PMID:[Fabry disease in 2004]. 1501 73

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).
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PMID:Fabry disease: a review. 1547 88

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.
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PMID:Renal variant of Anderson-Fabry disease and bilateral renal cell carcinoma. 1579 33

The prognosis of Fabry disease has changed since enzyme-replacement treatment was introduced. Therefore, early diagnosis is instrumental. We describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. A 35-year-old man was admitted because he was overweight and had hypertension, with a serum creatinine level of 1.3 mg/dL (115 micromol/L) and protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age of 32 years of acute myeloid leukemia, also had chronic renal failure and proteinuria, the diagnosis of Fabry disease was entertained. In the index patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and cornea verticillata suggesting Fabry disease were absent. Conversely, renal biopsy showed typical globotriaosylceramide deposits, and leukocyte alpha-galactosidase (alpha-GLA) A activity was decreased. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. In the brother who died, Fabry disease, missed at autopsy because of cancer-related findings, could be confirmed after repeated review of histological slides. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet). We conclude that familial chronic renal failure combined with proteinuria is suggestive of Fabry disease, and such specific mutations as E66K predominantly may affect the kidneys.
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PMID:Chronic renal failure and proteinuria in adulthood: Fabry disease predominantly affecting the kidneys. 1586 41

We report a 56-year-old man with history of chronic renal failure, who was diagnosed to have Fabry's disease after performing a percutaneous kidney biopsy. The diagnosis was confirmed by the deficient level of activity of alpha-galactosidase A and by the identification of the mutation. A enzime replacement therapy with alpha-galactosidase A was administered. After 18 months of treatment, a second kidney biopsy was performed showing renal deposits of globotriaosylceramide (we did not evaluate the percentage of histologic clearance of the deposits). Six months after the end of the therapy, a reduction in the impairment of renal function is observed, and the classic manifestations of the disease are absent.
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PMID:[Enzyme replacement therapy in Fabry's disease]. 1605 14

We report two cases of heterozygous Fabry disease with severe organ damage. Case 1 was a 47-year-old woman. In April 1977, at the age of 27 years, she had proteinuria and edema around the 26th week of her second pregnancy and was diagnosed as toxicosis of pregnancy. She had proteinuria after the delivery. In 1990, a renal biopsy showed zebra bodies under electron microscopic findings, and the patient was diagnosed as Fabry disease. In 1998, a myocardial biopsy showed identical findings. The patient developed severe hypertension and decreased renal function, and alpha-galactosidase enzyme replacement therapy was initiated. However, despite treatment, she was started on dialysis in 2004. Case 2 was a 40-year-old woman. In March 2003, the patient presented with severe hypertension. The patient had cerebral infarction, cardiac hypertrophy, old myocardial infarction and renal failure without diabetes mellitus, hyperlipidemia and collagen disease. The patient was diagnosed as Fabry disease from persistent numbness and pain in the four extremities, a family history of mortality due to heart disease, and skin biopsy findings. She is currently undergoing enzyme replacement therapy. It is generally known that female Fabry disease patients are asymptomatic or mildly symptomatic, as were the present two patients, but some can have marked organ disorders. Hence, even in female patients, it is necessary to consider Fabry disease as a causative disease of chronic renal failure.
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PMID:[Two cases of heterozygous Fabry disease]. 1691 64

Anderson Fabry disease (alpha galactosidase A deficiency) is an X-linked recessive lysosomal storage disorder; alpha galactosidase A deficiency results in accumulation of neutral glycosphingolipids, especially globotriaosylceramide (Gb3), in various cell types promoting development of disease with renal, cardiovascular, and cerebrovascular involvement. Clinical aspects which usually begin in childhood or adolescence include intermittent pain in the extremities (acroparesthesias), episodic "Fabry crisis" of acute pain lasting hours to days, characteristic skin lesions (angiokeratomas), hypohidrosis, heat and cold intolerance. Classic phenotype conception of the disease has changed within the past decade, recognizing that disease is not limited to the classical full-blown manifestation in affected males, but may also occur in carrier females. The expanding clinical spectrum of Anderson Fabry disease (AFD) is a real challenge to diagnosis, especially in some patients whose exclusive single organ manifestation belongs to the heart or kidney. This paper reviews natural history of three unrecognized cases recently diagnosed by markedly deficient alpha galactosidase A (alpha Gal A) activity in peripheral leucocytes. Case A: A male patient, aged 24 years, experienced recurrent acroparesthesia when he was 9 years-old. His 26 years-old sister has angiokeratomas as the only sign of disease (case B). Case C: the uncle of these two cases (A, B) has a long history of disease including chronic renal failure, bilateral deafness, stroke, aseptic osteonecrosis. The purpose of the presentation is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.
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PMID:Clinical spectrum of Anderson Fabry disease in a Romanian family. 1723

Fabry disease is a rare X-linked lysosomal storage disease leading to systemic involvement, mainly through GL-3 endothelial deposition. Initial symptoms may occur during childhood (acroparesthesia, angiokeratoma), prior to adulthood complications, i.e. renal, ocular, cerebral, neurological and cardiovascular involvement. An early diagnosis of the disease may be challenging because of a frequent atypical clinical presentation. Indeed, independent of conservative treatment (pain, proteinuria, chronic renal failure, arterial hypertension, heart failure, etc), enzyme therapy using recombinant alpha-galactosidase (agalsidase) has provided a safe pathophysiological approach, leading to significant organ functional improvement (mainly kidney and heart) and improved quality of life, which parallels tissue GL-3 clearance. Such a treatment is safe and efficient but its biweekly intravenous administration is still uncomfortable, so that further alternative therapeutic approaches may be encouraged.
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PMID:[Current management of Fabry disease]. 1737 18

Fabry disease (FD), the second most common type of lysosomal storage disease (LSD), is one of 41 disorders characterized by accumulation of substances normally degraded within lysosomes. It is an X-linked recessive disorder characterized by a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). The locus for human alpha-Gal A is located on the Xq22 chromosome. Most FD mutations are confined to a single family. Although FD is an X-linked disorder, up to one third of female carriers develop clinical manifestations of the disease. It typically presents during infancy or adolescence with crisis of neuropathic pain (acroparesthesia), angiokeratomas, and asymptomatic corneal lesions. As Gb3 deposition progresses, clinical manifestations occur in other organs. Patients typically die in the fourth or fifth decade of life due to cardiac, renal or cerebrovascular complications. Usually, there is diffuse deposition of glycosphingolipid in the renal glomeruli, tubules, interstitium, and vasculature. Clinically, the renal disease manifests with hypertension, microscopic hematuria (rare), moderate proteinuria, which can be in the nephrotic range, and lipiduria. End-stage renal disease can be treated with either dialysis or transplantation. Thegene for (x-Gal A was cloned and sequenced, which eventually led to production of enzyme for therapeutic use by either recombinant DNA technology or gene activation.
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PMID:Fabry kidney disease. 1765 9

The purpose of this review is first to describe the importance of early detection of vasopressin receptor mutations responsible for X-linked nephrogenic diabetes insipidus (NDI). We have proposed that all families with hereditary diabetes insipidus should have their molecular defect identified because early diagnosis and treatment of affected infants can avert the physical and mental retardation that results from repeated episodes of dehydration. Secondly, 95 published missense mutations responsible for X-linked NDI are likely to result in misfolded arginine-vasopressin V(2) receptors that are trapped in the endoplasmic reticulum. These misfolded receptors are unable to reach the plasma membrane in principal collecting duct cells and to engage the circulating antidiuretic hormone, arginine-vasopressin. These misfolded proteins potentially could be rescued with pharmacologic chaperones, an active area of research pertinent to other hereditary protein misfolding diseases such as cystic fibrosis, phenylketonuria, and Anderson-Fabry disease among many others. Finally, a long-term careful surveillance of all patients with hereditary NDI should be performed to prevent chronic renal failure likely caused by the long-term functional tract obstruction with reflux.
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PMID:Vasopressin receptor mutations in nephrogenic diabetes insipidus. 1851 85


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