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)

We describe a man and a woman with Fabry's disease. Renal biopsies showed late and early stages respectively of focal and segmental glomerulosclerosis (FSGS) and vascular changes. Clinically the hemizygous patient had advanced renal disease with nephrotic range proteinuria and serum creatinine 122 micromol/l. The female carrier had minimal albuminuria, borderline GFR with a normal serum creatinine, acroparesthesias, moderate fatigue, tinnitus and headache accompanied by ischemic cerebral lesions. Enzyme replacement therapy (ERT) was initiated according to our Fabry protocol, partly due to the renal morphologic findings. We conclude that FSGS and vascular changes may be an early morphologic finding in Fabry's disease, even in patients with subtle albuminuria. The potential role of FSGS as a marker of progressive renal disease in some Fabry patients is discussed. As FSGS and vascular changes obviously may exist across a wide range of clinical presentations and have potential prognostic implications, we suggest that a renal biopsy should be performed prior to enzyme replacement therapy in all adult Fabry patients with proteinuria of various levels. Efforts should be made to develop a scoring system to evaluate potential histologic markers. Protocol biopsies may have therapeutic implications and may provide valuable information in the evaluation of start and dosing of ERT.
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PMID:Focal and segmental glomerular sclerosis (FSGS) in a man and a woman with Fabry's disease. 1590 1

We report here the course and outcomes of 18-month enzyme replacement therapy in two 43 and 41-year-old brothers with Fabry disease. At 18 months of recombinant alpha-galactosidase A (Fabrazyme) infusions, we observed in the older patient: weight gain, decreased proteinuria (from 4 to 1.5 g/d), stabilization of creatinine clearance, much lower frequency and intensity of angina, and in the younger brother: weight gain, stabilization of creatinine clearance and proteinuria, prolongation of PQ interval and improvement of hearing. However, neurologic manifestations deteriorated over treatment period in both patients. No serious infusion-related side effects were observed.
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PMID:[First Polish experience with enzyme replacement therapy in patients with Fabry disease]. 1596 14

Anderson-Fabry disease (AFD) is a rare X-linked lipid storage disorder due to a deficient lysosomal a-galactosidase A (a-Gal) activity. In males with the classic form of the disease the enzymatic defect leads to progressive accumulation of glycosphingolipids (GL) in different organs, mainly in the kidney, heart, and brain, causing severe multisystem failure. AFD is usually mild in heterozygous females, but severe cerebrovascular, renal, and cardiac manifestations have been rarely described. The aim of this study is to describe renal involvement of mild symptomatic female carriers by ultrastructural analysis focusing to microvascular lesions, considered to be one of the major causes of systemic disease in AFD. Resin-embedded renal biopsies from 2 sisters with isolated mild proteinuria and belonging to a family group with AFD were observed by light and electron microscopy. In spite of the mild clinical symptoms, diffuse GL storages were demonstrated in all types of glomerular cells and in interstitial endothelial cells. Moreover, platelets were frequently observed in glomerular vassels, a feature coherent with a possible role of prothrombotic state, and platelet activation, in early glomerular lesions.
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PMID:Ultrastructural study of renal involvement in two females with Anderson-Fabry disease. 1603 75

Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient activity of alpha-galactosidase A (alpha-Gal A) resulting in the storage of glycosphingolipids, especially globotriaosylceramide (Gb3), in cells throughout the body, causing life-threatening renal, cardiac, and cerebrovascular complications in hemizygous males and some heterozygous females. Disease manifestations in heterozygotes are being recognized increasingly, but quantitative prospective data on their extent and severity are limited. Prospective clinical and laboratory assessments were performed in a 7-day study of 61 women with signs and symptoms of Fabry disease. Analyses included medical history and physical, neurologic, cardiac, and ophthalmologic assessments; laboratory assessments; renal function tests; magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head; and Fabry-related blood and urine tests, including Gb3 levels in blood and urine, skin biopsies, and DNA genotype analysis of the alpha-Gal A gene to identify causative mutations. Quality of life, pain and concomitant medication were documented using validated questionnaires and diaries. All patients had normal Gb3 levels in plasma; only 1 patient had visible storage material in the superficial dermal vascular endothelial cells. Cardiac, renal, or cerebrovascular abnormalities were documented in 52 of the 57 patients (91%) with confirmed Fabry genotypes. These included electrocardiographic abnormalities in 38 of 52 patients (73%), echocardiographic abnormalities in 8 of 57 (14%), proteinuria (>150 g protein/24-h urine) in 23 of 38 (61%), low estimated glomerular filtration rate (<90 mL/min per 1.73 m) in 24 of 57 (42%), abnormal MRI in 4 of 54 (7%), and abnormal MRA in 10 of 50 patients (20%). Angiokeratomas and corneal epitheliopathy were documented in 63% and 82% of the 57 patients, respectively. Despite the virtual absence of storage material in plasma and skin vascular endothelial cells, this population of women with Fabry disease exhibited a wide spectrum of clinical abnormalities. Useful outcome measures for assessment of specific therapies need to be developed. Studies limited to homogeneously affected subjects may be possible.
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PMID:The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. 1614 26

The authors present a patient with Fabry syndrome that remained undiagnosed for several years. Fabry syndrome is a genetic disease related to changes on the X chromosome. Its complex clinical presentation and diverse symptomatology is caused by deficient activity of lysosomal hydrolase alpha-galactosidase enzyme. Defect in the basic alpha-galactosidase molecule implies genetic change, which can be a predisposing factor for the development of atypical and typical forms of this genetic disease. In the presented case, clinical manifestation and hemizygous symptomatology were the evidence of metabolic and genetic irregularity, typical clinical presentation of Fabry disease. Many authors report generalized vasculopathy as a basic characteristic of Fabry disease and a causative factor of multiorgan changes. Some authors indicate that persons with diagnosed asymmetric hypertrophy of the left ventricle have decreased alpha-galactosidase. Cardiac complications, coronary disease, and acute myocardial ischemia are often present in cases of Fabry disease, frequently causing death in such patients. Characteristic central nervous system symptoms with skin-burning sensation and paresthesia were also present in our case. Cerebrovascular complications were caused by changes on small blood vessels. Clinical signs of renal failure were nonspecific, and the diagnosis was based on extrarenal symptoms. Initial renal manifestations were insignificant as asymptomatic proteinuria and microhematuria, due to which our patient was referred to further examination. The level of alpha-galactosidase was significantly decreased. The severity and progression of this disease depends on the level of alpha-galactosidase enzyme in serum and its catabolic effect. More recent studies have showed that deficient enzyme can be synthetic zed and, accordingly our patient has been successfully enrolled in the replacement therapy program.
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PMID:Fabry disease--a diagnostic and therapeutic problem. 1635 Aug 34

Fabry disease is an inherited metabolic disease caused by the deficiency of the lysosomal enzyme alpha-Galactosidase A. In consequence, globotriaosylceramide (Gb3) accumulates in nearly all tissues and body fluids. Typically, the disease manifestation is in childhood with acroparaesthesia of burning character in hands and feet. Angioceratoma, cornea verticillata and proteinuria may be found as well at an early stage of the disease. With ongoing age vital organs are increasingly affected. Major causes for death are cerebrovascular events, myocardial infarction, and progressive renal insufficiency. Enzyme replacement therapy (ERT) offers an efficient treatment of Fabry disease. On the basis of newly diagnosed patients we describe the clinical picture, diagnosis and principles of ERT.
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PMID:[Fabry disease--a provocation for pediatrics]. 1643 75

Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r-halphaGalA) enhances microvascular globotriaosylceramide clearance and improves clinical symptoms in patients with Fabry disease. We evaluated whether these effects are translated into a long-term benefit of kidney and heart function. We did a single center, prospective, open label study in 26 patients with Fabry disease (one early death, follow-up in 25 patients). r-Alpha-GalA was administered in a dosage of 1 mg/kg body weight every second week. The effect of therapy on clinical end points (death, cardiac and cerebrovascular event, renal failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc-GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8 months, nine patients experienced 12 end points, including two deaths. All end points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17 ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23 ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without impairment of renal function (n = 9) had a more favorable outcome (no clinical events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and 10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01 +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less favorable outcome and may develop cardiovascular and renal end points despite ERT.
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PMID:Clinical benefit of enzyme replacement therapy in Fabry disease. 1660 85

Fabry disease is a lysosomal storage disorder with kidney involvement. The initial manifestation of kidney disease is often impaired urinary concentrating ability in adolescence or young adulthood. We describe a boy diagnosed prenatally with Fabry disease who presented with polyuria, polydipsia, hypertension, hypokalaemia and proteinuria at 7 years of age. A formal water-deprivation test followed by vasopressin challenge confirmed nephrogenic diabetes insipidus. A renal biopsy revealed findings typical of Fabry disease. Angiotensin converting-enzyme therapy resulted in rapid improvement of symptoms, normalization of blood pressure and resolution of hypokalaemia and proteinuria. This child is the youngest reported Fabry disease patient with documented renal pathology and clinical manifestations of hypertension, proteinuria and nephrogenic diabetes insipidus.
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PMID:Fabry disease and nephrogenic diabetes insipidus. 1672 92

Fabry disease is a metabolic disorder caused by the genetic deficiency of alpha-galactosidase A. Deposition of glycosphingolipids in podocytes, endothelial cells, and other cell types leads to formation of myelin-like inclusions, which are the hallmark of the disease. In most untreated males, the disorder progresses to end-stage kidney disease. Fabry disease is rare, and no renal biopsy series focusing on pathologic findings has been published in the past 25 years. We retrieved kidney biopsies diagnosed with Fabry disease from our files, and reviewed clinical data as well as the light and electron microscopy. In total, 11 patients were identified: six male subjects aged 17-43 years and five female subjects aged 30-73 years. On average, male patients presented more than 10 years earlier then female patients. A total of 10 patients had proteinuria, two with the nephrotic syndrome. Four male and three female patients had decreased renal function. Light microscopy showed vacuolization of the podocyte cytoplasm and variable glomerular sclerosis. Older patients and males had more advanced glomerular and interstitial sclerosis, but three of the five female patients also had advanced renal disease. Electron microscopy showed the characteristic myelin-like inclusions most prominently in the podocyte cytoplasm. Seven patients also had podocyte foot process effacement. A second type of deposit, unexpected and conspicuous, was identified in three males, and found to be associated with glomerular basement membrane duplications. These deposits were composed of layered membrane-like material, and therefore morphologically distinct from myelin-like inclusions. They probably represent remnants of damaged endothelial cells.
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PMID:Fabry disease: a morphologic study of 11 cases. 1679 80

We report a 16-year-old girl and her one-year-younger sister, both heterozygous for the c.34del24 mutation of the GLA (alpha-galactosidase A) gene, which they inherited from their father who is affected by Fabry disease (FD). Both girls presented with macrohematuria and rapidly progressing proteinuria. Urine analysis revealed glomerular hematuria and a nephrotic range of proteinuria suggesting a concomitant glomerulonephritis. Light microscopy of kidney biopsy was characteristic of IgA nephropathy (IgA deposits in mesangial areas and glomerular capillary loops, and mesangial hypercellularity), whereas electron microscopy showed changes typical of Fabry disease (multiple osmiophilic inclusions in the subendothelial and mesangial areas). These two cases and similar reports in the literature suggest that IgA nephropathy in FD is not merely coincidental.
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PMID:IgA nephropathy in two adolescent sisters heterozygous for Fabry disease. 1683 83


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