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)

The association of nephronophthisis and tapeto-retional degeneration was described by both Senior and Loken in 1961, but prior to 1974 only 28 cases had been published. This report describes 8 new cases in 27 members of 5 families. The severe juvenile type produces blindness in infancy and death from renal failure before the age of ten. The adult type is characterized by later onset, slower progression of the renal disease and milder ocular manifestations. The eye disease may be congenital amaurosis of Leber type, pigmentary retinal degeneration or retinitis punctata albescens and the electroretinogram (ERG) is of value in the diagnosis of these varieties of hereditary tapeto-retinal degeneration. Renal involvement is often asymptomatic. Defective urinary concentration leading to polyuria and polydipsia is the earliest sign. Proteinuria is inconstant and urinary sediment is often normal. Two patients had aminoaciduria. The disease progresses inexorably to chronic renal failure. One patient has been successfully transplanted and two others are on chronic hemodialysis. Renal histological changes are those of nephronophthisis with tubulointerstitial lesions and multiple cysts. Senior-Loken syndrome appears to be transmitted by a single autosomal recessive pleotropic gene of variable expression. Degeneration of neuroepithelium and renal tubular epithelium, both tissues of ectodermal origin, may represent a genetically determined enzyme abnormality.
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PMID:Senior-Loken syndrome (nephronophthisis and tapeto-retinal degeneration): a study of 8 cases from 5 families. 124 84

Familial LCAT deficiency is due to deficiency of plasma lecithin-cholesterol acyltransferase. The plasma is rich in free cholesterol and lecithin while cholesterol ester and lysolecithin levels are reduced. Analysis of the abnormal lipoproteins has helped our understanding of plasma lipid and lipoprotein metabolism in normals and in patients with liver disease. Proteinuria and anaemia are common and there is marked corneal lipid deposition. Eventually renal function deteriorates and dialysis and/or renal transplantation may be necessary. The human LCAT gene has been sequenced and been shown to be present on chromosomal segment 16q22-the region predicted on the basis of recombination studies as the site of the LCAT deficiency gene. The gene defect has been identified in some cases, but the mechanism remains unclear as the mutations were not in the region presumed to be the enzyme's active site. Only three cases of fish-eye disease have been described; all were elderly and had obvious corneal opacities. They had fasting hypertriglyceridaemia and increased VLDL. IDL and LDL were increased and were triglyceride rich. HDL, reduced by 90%, was mainly HDL3--with a high free and low ester cholesterol. LCAT activity in fish-eye plasma was normal but when measured in an exogenous substrate it was only 10-15% of normal. Fish-eye HDL is a substrate for purified LCAT, but fish-eye LCAT does not esterify free cholesterol of HDL (normal or fish-eye), although it esterifies free cholesterol of VLDL and LDL. It has been suggested that one type of LCAT activity acts on HDL (alpha-LCAT) and another on VLDL and LDL (beta-LCAT)--and that fish-eye disease is due to alpha-LCAT deficiency, and classical familial LCAT deficiency due to lack of both components.
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PMID:Familial LCAT deficiency and fish-eye disease. 314 86

Since diabetes is a major health problem in Malta a study was conducted to gain a better insight into one of its most common complications, that of retinopathy. A random sample of 200 cases of adult onset diabetes with retinopathy who attended the main hospital's diabetes clinic was assessed by an experienced ophthalmologist. Non-proliferative retinopathy was subdivided into three degrees of severity according to the number of microaneurysms, haemorrhages, exudates, and intraretinal microvascular abnormalities present while proliferative retinopathy included also advanced eye disease. Data on medical and family histories was gathered from personal interrogation and counterchecked from hospital files. A medical examination searched for other concomitant disease. The 124 females and 73 males were similarly aged with a mean of 59.5 +/- 11.5 years. The mean age at onset of diabetes was 44.4 +/- 7.9 years: no significant differences were seen between the grades of retinopathy or the sexes. Onset of eye disease was first detected at a mean age of 56.9 +/- 7.0 years. The great majority (82%) of retinopathy cases occurred after 10 years of diabetes. Males appeared to develop eye disease (especially non-proliferative) at a younger age (53.4 +/- 7.6 vs 58.9 +/- 6.6 years, p < 0.01) and after a shorter duration of diabetes (10.1 +/- 6.6 vs 14.0 +/- 7.8 years, p < 0.001) than females. Severity of retinopathy was strongly associated (p < 0.001), in females rather more than in males, with poor glycaemic control, use of insulin, presence of proteinuria and decreasing vision; and less markedly (p < 0.01) with duration of diabetes of more than 10 years, neuropathy and glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retinopathy in Maltese type 2 diabetic patients. 764 10

X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.
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PMID:Characterization of carrier females and affected males with X-linked recessive nephrolithiasis. 770 83

Familial plasma lecithine: cholesterol acyltransferase (LCAT) deficiency is a disease that is inherited as an autosomal recessing trait. The main clinical abnormalities are corneal opacities, anemia and frequently, though not invariably, proteinuria. These abnormalities result from a failure of LCAT to esterify cholesterol in plasma. Renal failure can be a life-threatening complication. In plasma, all lipoprotein classes show abnormalities including lipid composition, shape, distribution and concentration. Fish eye disease, which is characterized by corneal opacities and plasma lipoprotein abnormalities, is also a result from deficiency of LCAT activity. As LCAT gene has been cloned, molecular defects of both familial LCAT deficiency and fish eye disease have been reported recently.
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PMID:[Familial LCAT deficiency]. 785 12

An apparent epidemic of diabetes is occurring in adults worldwide. This trend seems to be associated with socioeconomic and lifestyle changes. The population of developing countries and some communities within developing countries are at higher risk. Diabetic eye disease and its complications, especially diabetic retinopathy, are a leading cause of blindness and visual dysfunction in adults in economically developed societies. Epidemiological studies of the impact of diabetic eye disease in developing countries are scarce. Risk factors for the development and progression of diabetic retinopathy include, among others, hyperglycemia, genetic factors, race, duration of the disease, arterial hypertension, and proteinuria.
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PMID:The epidemiology of diabetes mellitus and diabetic retinopathy. 960 35

The aim was to study the quality of care at a diabetic clinic of a large hospital in Sri Lanka; a sample of 200 patients was randomly selected. A questionnaire was designed to assess patient knowledge of diabetic management and service provision. Clinic attendance records were also used. Measures of outcome were taken to be (i) the patient's level of understanding of their condition, (ii) the availability of diagnostic tests, (iii) the provision of regular screening and (iv) the length of consultation time. The average attendance at each four-hour clinic was 174 patients. With three doctors available, average consultation time was four minutes per patient. Procedures undertaken included measuring blood glucose levels, testing for proteinuria and screening for hyperlipidaemia, hypertension and eye disease. The average score for knowledge regarding management and complications, obtained from analysis of the questionnaire, was 5.3 out of a maximum of 9.0 points. The study showed that the quality of care of diabetic patients did not meet the standards that should be expected. Two of the principal problems were lack of good organisation and poor planning of resource utilisation. An increase in funding would, of course, assist in implementing the improvements suggested.
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PMID:Study of the quality of care at a diabetic clinic in Sri Lanka. 1107 4

The esterification of free cholesterol (FC) in plasma, catalyzed by the enzyme lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), is a key process in lipoprotein metabolism. The resulting cholesteryl esters (CE) represent the main core lipids of low (LDL) and high density lipoproteins (HDL). Primary (familial) LCAT-deficiency (FLD) is a rare autosomal recessive genetic disease caused by the complete or near absence of LCAT activity. In fish-eye disease (FED), residual LCAT activity is still detectable. Here, we describe a 32-year-old patient with corneal opacity, very low LCAT activity, reduced amounts of CE (low HDL-cholesterol level), and elevated triglyceride (TG) values. The lipoprotein pattern was abnormal with regard to lipoprotein composition and concentration, but distinct lipoprotein classes were still present. Despite of typical features of glomerular proteinuria, creatinine clearance was normal. DNA sequencing and restiction fragment analyses revealed two separate mutations in the patient's LCAT gene: a previously described G to A transition in exon 4 converting Arg140 to His, inherited from his mother, and a novel G to C transversion in exon 2 converting Gly71 to Arg, inherited from his father, indicating that M.P. was a compound heterozygote. Determination of enzyme activities of recombinant LCAT proteins obtained upon transfection of COS-7 cells with plasmids containing G71R-LCAT or wild-type LCAT cDNA revealed very low alpha- and absence of beta-LCAT activity for the G71R mutant. The identification of the novel G71R LCAT mutation supports the proposed molecular model for the enzyme implying that the "lid" domain at residues 50-74 is involved in enzyme:substrate interaction. Our data are in line with the hypothesis that a key event in the etiology of FLD is the loss of distinct lipoprotein fractions.
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PMID:Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease. 1621 49

The use of intravitreal injections of anti-Vascular Endothelial Growth Factor (anti-VEGF) has been used for a broad spectrum of ocular pathologic entities. Although the dose of anti-VEGF agents used for treating eye disease is minute compared with that used intravenously, intraocular administration can lead to systemic absorption and reduce serum VEGF levels. Several systemic side effects, such as hypertension and cardiovascular complications have been rarely reported in the literature. Renal complications of intravenous administration of anti-VEGF, are well known and include a variety of renal pathological damage which can induce proteinuria and hypertension. We describe herein, 2 cases of diabetic patients with preexisting kidney disease who presented severe reduction of their renal function after intraocular administration of anti-VEGF. Although a cause -effect correlation cannot be established unless further studies are performed, we believe that pretreatment counseling should include a discussion outlining the possible risk of aggravating of the renal function in patients with kidney disease. Close cooperation with the patient's nephrologist and close monitoring of the patient may be required, in such cases, in order to monitor the renal function before and after the intravitreal administration of anti-VEGF.
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PMID:Renal injury following intravitreal anti-VEGF administration in diabetic patients with proliferative diabetic retinopathy and chronic kidney disease--a possible side effect? 2451 9

Renal coloboma syndrome (RCS) is a rare inherited condition exhibiting a variable clinical phenotype of renal and ocular abnormalities. In 50% of cases, mutations can be found in the transcription factor PAX2. We present three generations of a family with a PAX2 mutation who showed variable eye and renal phenotypes. Renal phenotypes ranged from normal kidneys with the absence of proteinuria to end-stage renal disease (ESRD) at 17 years of age. Eye phenotypes included the typical morning glory anomaly, macular retinal pigment epithelial changes and retinal venous tortuosity. We identified a PAX2 mutation c.228_251dup [p.Ser77_Gly84dup] which segregated with the phenotype in an autosomal dominant fashion. A molecular genetic diagnosis allowed identification and management of at-risk family members. Given the phenotypic variability, clinicians need to consider the possibility of RCS in patients with a family history of chronic kidney disease (CKD) or eye disease.
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PMID:A wide spectrum of phenotypes in a family with renal coloboma syndrome caused by a PAX2 mutation. 2729 69


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