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 25-year-old man with Fabry disease who remained undiagnosed until progressive renal involvement had begun, because of few clinical signs or symptoms except intermittent acroparesthesia. He had non-nephrotic proteinuria and normal renal function. Renal biopsy revealed focal and segmental glomerular sclerosis with vacuolated podocytes. Electron microscopy demonstrated characteristic lamellated bodies. Alpha-galactosidase A (alpha-galA) activity was markedly decreased. Early diagnosis of Fabry disease is becoming important because of the prospect of recombinant alpha-galA replacement therapy. Careful history taking, physical examinations, and renal histology with electron microscopy are essential for the diagnosis in the course of the disease.
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PMID:Fabry disease with few clinical signs and symptoms. 1248 56

A 40-year-old man with Fabry disease, confirmed by decreased leukocyte alpha-galactosidase A activity in 2001, complained of sudden bilateral deafness, as evidenced by clinical history and audiometry. Magnetic resonance of the brain revealed features typical of Fabry disease. Other clinical manifestations of the disease included: angiokeratoma, mild proteinuria with normal renal function, lymphoedema of the lower limbs, pre-excitation syndrome, myocardial hypertrophy.
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PMID:[Atypical symptoms of Fabry's disease: sudden bilateral deafness, lymphoedema and Lown-Ganong-Levine syndrome]. 1268 50

Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). The lack of alpha-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosyceramide (GL3). Affected organs include, among others, the vascular endothelium, heart, brain, and kidneys, leading to end-stage renal disease (ESRD). Since Fabry disease cannot be cured at present, clinical management is symptomatic. Enzyme replacement therapy (ERT) with recombinant alpha-Gal A has been introduced as a new therapeutic option for the treatment of Fabry patients. Short-term (one year) clinical studies have positively correlated ERT with improvement of clinical symptoms and microvascular endothelial cell clearance. Treatment outcome concerning severe organ manifestations such as proteinuria and renal function impairment, left ventricular hypertrophy, and heart failure in the long run has yet to be shown. In our studies we used sensitive and noninvasive techniques such as ultrasound-based strain rate imaging and magnetic resonance imaging (MRI), combined with MR-spectroscopy (MR-S), for the quantification of functional abnormalities at an early stage of the disease and during long-term follow-up. Future issues should determine the appropriate timing to start therapy and how children and heterozygous females should be managed. Given the diagnostic and therapeutic potential today, it is of importance to identify patients at an early stage and to start therapeutic intervention before progression of organ damage is inevitable.
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PMID:Fabry disease: diagnosis and treatment. 1269 40

Fabry's disease is an x-linked, recessive, lysosomal storage disorder that results from deficient alpha-galactosidase A activity with pathological sphingolipid deposition mainly in endothelium, smooth muscle cells, kidneys, central and peripheral nervous system, and myocardium. Clinical manifestation mostly occurs during childhood and adolescence with severe pain attacks or chronic pain mainly in hands and feet, hypohydrosis, and skin lesions (angiokeratoma). In more advanced disease stages, renal and cerebrovascular complications develop with proteinuria and later renal failure and cerebral ischemia caused by cerebral microangiopathy, dilatative arteriopathy, or cardiac embolism. Heterozygote female carriers are severely affected more often than was previously considered. The diagnosis is based on the detection of deficient alpha-galactosidase A activity in leukocytes, fibroblasts, or tissue biopsies. Two randomised placebo-controlled studies showed that enzyme replacement is effective by demonstrating either reduced pain or reduced tissue sphingolipid deposition. Early diagnosis of Fabry's disease is important in view of these new causal therapeutic options.
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PMID:[Fabry's disease: new therapeutic options for this lysosomal storage disorder]. 1279 87

In men with classical Fabry disease (alpha-galactosidase A [alpha-Gal A] deficiency), kidney failure occurs as early as the second decade of life. In contrast, men with the mild "cardiac variant" have late-onset cardiac involvement and proteinuria but usually do not have renal failure. To investigate the nature of renal involvement in the cardiac variant of Fabry disease, the renal function and morphology were assessed in a 75-year-old affected man. He had mild congestive heart failure, a reduced left ventricular ejection fraction, and hypercholesterolemia but lacked the classical Fabry disease manifestations, including angiokeratoma, acroparesthesias, corneal and lenticular opacities, and hypohidrosis. At age 75 years, he had significant proteinuria, and mildly decreased renal function (serum creatinine, 1.8 mg/dL [159 micromol/L]), presumably secondary to hypertensive arteriosclerosis. He had about 4% residual alpha-Gal A activity in leukocytes, and mutation analysis identified the N215S missense mutation, the common lesion in cardiac variants. Histologic and ultrastructural studies of kidney tissue showed that lysosomal glycosphingolipid deposition was extensive in podocytes, rare in tubular epithelial cells, and absent in mesangial, interstitial, and vascular endothelial and smooth muscle cells. This cardiac variant serves as an "experiment of nature" showing that the residual alpha-Gal A activity precludes glycosphingolipid deposition in the renal endothelial and other cells that lead to early renal failure in classically affected men, whereas marked podocyte accumulation is associated with proteinuria and possibly late-onset renal dysfunction. These findings have important implications for the renal effectiveness of enzyme replacement therapy in classically affected patients and for the aggressive treatment of proteinuria in Fabry disease.
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PMID:Fabry disease: renal involvement limited to podocyte pathology and proteinuria in a septuagenarian cardiac variant. Pathologic and therapeutic implications. 1471 41

We present a patient with Fabry disease with remarkable diagnostic findings and gluten-sensitive enteropathy. An 11-year-old girl was admitted to hospital with weight loss, anorexia, nausea, vomiting, flank pain, acroparesthesia, and painful extremities. Her mother had end-stage renal failure secondary to Fabry disease. On physical examination, she had growth retardation. Ophthalmological examination showed characteristic whorl-like corneal opacities and Fabry disease was confirmed with low alpha-galactosidase A (alpha-gal A) activity. Her painful attacks were treated with carbamazepine, but vomiting and nausea continued. Laboratory studies revealed positive serum anti-endomysium and anti-gliadin antibodies. Small intestinal biopsy showed subtotal villous atrophy compatible with gluten-sensitive enteropathy. Following treatment with a gluten-free diet, her gastrointestinal symptoms completely disappeared within a few weeks and then she had catch-up growth. In her long-term follow-up, proteinuria appeared and renal involvement was confirmed by characteristic renal biopsy findings. Following these clinicopathological findings, enzyme replacement therapy was started. In conclusion, although heterozygous females can be asymptomatic or are expected to have a mild course of the disease, a severe clinical course in our patient in the 2nd decade is of particular interest. In addition, Fabry disease occurring with gluten-sensitive enteropathy, a very rare co-existence, is emphasized.
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PMID:The co-existence of Fabry and celiac diseases: a case report. 1508 21

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

A 65-year-old man presented to our institution for workup of proteinuria. His serum creatinine level was 1.7 mg/dL (130 micromol/L), and he had proteinuria with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney biopsy and low serum and leukocyte levels of alpha-galactosidase A. Review of his history, family history, physical examinations, and diagnostic studies did not show other findings typical of this disease. His renal function continued to decline, and he eventually underwent a living unrelated renal transplantation 5 years later. Three years after transplantation, his creatinine level is 1.7 mg/dL (130 micromol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m2 . Genetic studies showed that he has a novel missense mutation (M42L) in exon 1. Methionine at codon 42 is highly conserved in eukaryotic alpha-galactosidase A orthologues. This genotype predicts a minor misfolding of alpha-galactosidase A because of a small difference in hydrophobicity between methionine and leucine. His mutation resulted in a very low, but detectable, serum level of alpha-galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry disease that present with predominantly renal manifestations are rare and require a high index of suspicion for diagnosis. Because treatment for Fabry disease recently has become available, it is important for clinicians to be aware of this disease and pursue the diagnosis in cases of otherwise unexplained renal dysfunction.
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PMID:A novel alpha-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease. 1549 42

Fabry disease is an under-recognized X-linked recessive lysosomal storage disorder resulting from the deficient activity of the enzyme alpha-galactosidase A (alpha-Gal A). The first case of Fabry disease in Slovenia was diagnosed in 1991. This 46 year-old male was referred for dermatologic evaluation of a purpura on his abdomen. He was being treated for proteinuria and cardiac symptoms. The diagnosis of angiokeratoma corporis diffusa (Fabry disease) was made clinically and confirmed by demonstration of the deficient leukocyte alpha-Gal A activity. The patient subsequently developed cerebrovascular symptoms, coronary disease, and renal failure, and died from a recurrent myocardial infarction. Family studies identified several other affected males and carrier female relatives with this X-linked recessive disorder. This case illustrates the typical multi-manifestations of this inherited disease which now can be safely and effectively treated by enzyme replacement therapy. Early diagnosis is important for the most effective treatment of this disease.
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PMID:Fabry disease. A case report. 1581 41

A 16-year-old Japanese girl was admitted to our hospital on February 27, 2001, for acute renal failure. She had not shown proteinuria or hematuria in any school examination through 2000. The first renal biopsy specimen showed focal segmental glomerulosclerosis and tubulointerstitial change. Electron microscopy showed numerous myeloid bodies in the glomerular epithelium suggesting the diagnosis of Anderson-Fabry disease. After electron microscopy, we measured WBC alpha-galactosidase A, which was slightly decreased to 36.1 nmol/mg P/h (normal: 49.8 - 116.4). WBC alpha-galactosidase A levels for other family members were 74.3 for the mother, 4.8 for the father, 45.6 for the elder sister, and 16.3 for the younger sister. During the follow-up, she had two episodes of nephrotic syndrome, which responded well to steroid therapy. Both second and third renal biopsy showed numerous myeloid bodies by electron microscopy. A 52-year-old man, the father of the case one patient, was admitted for renal biopsy because of proteinuria and low levels of WBC alpha-galactosidase. Biopsy specimen showed typical changes under light microscopy and typical myeloid bodies by electron microscopy. Our cases underscore the importance of electron microscopy when examining the biopsy specimen and suggest that undiagnosed Anderson-Fabry disease may be present, in particular on chronic dialysis.
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PMID:Two unusual cases of Anderson-Fabry disease in a Japanese family. 1590


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