UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi complex. Several mutations were reported in patient's OCRL gene leading to enzyme deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo mutation in exon 10. The patient aged of 19 months was referred to our medical centre because of a psychomotor retardation. He had a medical history of eye abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5 weeks old. Cataract has been treated after chirurgical therapy but ocular hypertonia persisted. Physical examination revealed an axial hypotonia and walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L), a slight decrease of serum phosphate level (24 mg/L) and an increased serum phosphatase activity. Further studies showed mild proteinuria, urinary bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical and biological data, Lowe syndrome has been suggested. In this context, molecular investigation has been performed using dHPLC/sequencing techniques which allow identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10 of the OCRL gene. The mutation was not found in the probant's mother suggesting a neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations have been reported, variations were noted concerning their localization as well as their type. To our knowledge, this is the first report of the neo mutation c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in a Moroccan patient.
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PMID:[Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]. 1642 Sep 90

Alport syndrome (AS) is a hereditary glomerulonephritis variably associated with neural hearing loss and ocular abnormalities. The prevalence of the disease is estimated at approximately 1 in 50,000 live births. AS arises from mutations in genes encoding alpha chains constituting type IV collagen. In 85% of patients, the disease results from mutations in the COL4A5 gene located on X chromosome. In the hemizygous male, persistent microhematuria is present from early life, then proteinuria and renal insufficiency occur with time, leading to end-stage renal failure before age 40. In the heterozygous female, clinical manifestations vary from completely healthy state to end-stage renal failure, most often reached after the age of 40. In 15% of patients, the disease results from mutations in either the COL4A3 or the COL4A4 gene, both located on chromosome 2. When both alleles are mutated (autosomal recessive form), the phenotype is constantly severe, resembling that of the hemizygous male in the X-linked form. In the heterozygous individual, the clinical spectrum vary from the absence of any manifestation to the development of proteinuria - the so-called autosomal-dominant AS -, and even renal insufficiency, sometimes reaching end-stage (after the age of 40) through the most frequently encountered phenotype, i.e. a persistently isolated microhematuria, accounting for the so-called benign familial hematuria (or healthy carrier state). The determinants of the phenotype remain largely unknown, so that it may be risky to predict renal prognosis in the individual with a single COL4A3/A4 mutation and an isolated microhematuria at the time of examination.
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PMID:[From Alport syndrome to benign familial hematuria: clinical and genetic aspect]. 1689 72

Mutations in the gene encoding ClC-5 lead to X-linked hypercalciuric nephrolithiasis (XLHN), characterized by proteinuria, hypercalciuria, and phosphaturia. In renal proximal tubule cells, ClC-5 was identified as an important player in endocytosis, which ensures reabsorption of filtered protein. However, the recent finding that ClC-5 is a Cl(-)/H(+) antiporter and not a Cl(-) channel as long thought points to the lack of understanding of its functional role. Also, little biochemical data are available about ClC-5 and its post-translational modifications have not been investigated. Here, we examined the role of N-glycosylation of xClC-5 in the Xenopus oocyte expression system by comparing wild-type (WT) xClC-5 and N-glycosylation site mutants. We found that xClC-5 is N-glycosylated on asparagines 169 and 470, which are the only N-glycosylated sites. xClC-5 mutants have an increased susceptibility to polyubiquitination and proteasomal degradation; however, without a notable impact on the expression level. Using a cross-linking reagent, we showed that xClC-5 assembles into protein complexes, independent of its N-glycosylation. Voltage-clamp measurements showed a reduced conductance in the presence of tunicamycin and with xClC-5 N-glycosylation site mutants. Using immunocytochemistry, we localized xClC-5 mainly in intracellular compartments, and found that its cell surface pool is reduced in the absence of N-glycans. We further examined the plasma membrane retrieval of WT and mutant xClC-5 in the presence of Brefeldin A (BFA), and found that the non-glycosylated mutant was retrieved more than five times faster than the WT protein. We conclude that N-glycosylation enhances cell surface expression of xClC-5, increasing its plasma membrane transport activity.
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PMID:N-glycosylation of the Xenopus laevis ClC-5 protein plays a role in cell surface expression, affecting transport activity at the plasma membrane. 1711 67

Alport syndrome (AS) is the most common form of hereditary nephritis. Females with X-linked AS are heterozygous carriers of the disease mutation. Carrier status in females without a family history has traditionally been diagnosed by kidney biopsy; more recently skin biopsy has been utilized. We report on a 14-year-old girl with long-standing hematuria and intermittent proteinuria who underwent kidney and skin biopsy to establish a definitive diagnosis. Electron microscopy showed extensive thinning of glomerular basement membrane (GBM), with no evidence of lamination. Immunofluorescence staining showed continuous GBM staining for the alpha3(IV) and alpha5(IV) collagen chains, whereas the epidermal basement membrane showed discontinuous alpha5(IV) collagen staining consistent with an X-linked carrier of AS. Few reports have shown discordance between kidney and skin biopsy findings as seen in this case, presumably due to X chromosome lyonization. We therefore suggest that simultaneous kidney and skin biopsies may be more accurate in the assessment of potential female carriers of AS than either kidney biopsy or skin biopsy alone.
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PMID:Discordance between skin biopsy and kidney biopsy in an X-linked carrier of Alport syndrome. 1729 21

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

Alport syndrome (AS) is a progressive hereditary glomerulonephritis presented with hematuria, progressive renal failure, sensorineural deafness, and ocular lesions. Females with X-linked Alport syndrome (XLAS) have variable phenotypes, from asymptomatic hematuria to renal failure. In order to understand the possible mechanism of different phenotypes in female XLAS, we analyzed mRNA expression level of the mutant COL4A5 gene in fibroblasts, the X-inactivation pattern in peripheral blood DNA, and the phenotype variability of XLAS females. Total RNA was isolated from cultured skin fibroblasts in five females with XLAS and confirmed deletion mutations of COL4A5 mRNA. Reverse transcription-polymerase chain reaction (PCR) was performed to amplify the fragment, including the mutation sequences of the COL4A5 gene. The PCR products were electrophoresed with 8% polyacrylamide gel. Messenger RNA expression level of the mutant COL4A5 gene was analyzed with the optical density of PCR product revealed under polyacrylamide gel. The X-inactivation analysis was performed using HpaII predigestion of peripheral blood DNA followed by PCR of the highly polymorphic CAG repeat of the androgen receptor (AR) gene. All patients in the study had persistent microscopic hematuria. Two of them had gross hematuria. Three cases had persistent and severe proteinuria of 2+~3+, and the others had discontinuous and milder proteinuria of - ~+. The patients whose mRNA expression level of the mutant COL4A5 gene was higher had persistent and more severe proteinuria (r = 0.975, P = 0.005). None of them had skewed X inactivation. Our preliminary results demonstrate that the quantity of mRNA expression level of the mutant COL4A5 gene was correlated with the phenotypic severity of females with XLAS, and this could not be explained by X-inactivation pattern in peripheral blood leukocytes.
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PMID:Correlation between mRNA expression level of the mutant COL4A5 gene and phenotypes of XLAS females. 1746 60

The renal Fanconi syndrome is a defect of proximal tubular function causing aminoaciduria and low-molecular-weight proteinuria. Dent's disease and Lowe syndrome are defined X-linked forms of Fanconi syndrome; there is also an autosomal dominant idiopathic form (ADIF), phenotypically similar to Dent's disease though its gene defect is still unknown. To assess whether their respective gene products are ultimately involved in a common reabsorptive pathway for proteins and low-molecular-mass endogenous metabolites, we compared renal Fanconi urinary proteomes and metabonomes with normal (control) urine using mass spectrometry and (1)H-NMR spectroscopy, respectively. Urine from patients with low-molecular-weight proteinuria secondary to ifosfamide treatment (tubular proteinuria; TP) was also analyzed for comparison. All four of the disorders studied had characteristic proteomic and metabonomic profiles. Uromodulin was the most abundant protein in normal urine, whereas Fanconi urine was dominated by albumin. (1)H-NMR spectroscopic data showed differences in the metabolic profiles of Fanconi urine vs. normal urine, due mainly to aminoaciduria. There were differences in the urinary metabolite and protein compositions between the three genetic forms of Fanconi syndrome: cluster analysis grouped the Lowe and Dent's urinary proteomes and metabonomes together, whereas ADIF and TP clustered together separately. Our findings demonstrate a distinctive "polypeptide and metabolite fingerprint" that can characterize the renal Fanconi syndrome; they also suggest that more subtle and cause-specific differences may exist between the different forms of Fanconi syndrome that might provide novel insights into the underlying mechanisms and cellular pathways affected.
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PMID:Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome. 1749 94

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

Renal stone disease (nephrolithiasis) affects 5% of adults and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in more than 35% of patients, and may occur as a monogenic disorder, or as a polygenic trait involving 3 to 5 susceptibility loci in man and rat, respectively. Studies of monogenic forms of hypercalciuric nephrolithiasis in man, for example, Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels, and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal recessive disease, is caused by mutations of the bumetanide-sensitive Na-K-Cl (NKCC2) cotransporter, the renal outer-medullary potassium channel (ROMK), the voltage-gated chloride channel, CLC-Kb, or in its beta subunit, Barttin. Dent's disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis, is due to mutations of the chloride/proton antiporter, CLC-5; ADHH is associated with activating mutations of the calcium-sensing receptor, which is a G protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium-phosphate cotransporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to kidney stones and bone disease.
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PMID:Genetics of hypercalciuric nephrolithiasis: renal stone disease. 1787 84

Anderson-Fabry disease (AFD) is a rare, X-linked lysosomal storage disease that leads to progressive intracellular accumulation of globotriaosylceramide in visceral organs and the vascular endothelium. We report two patients with end-stage renal disease who received renal allograft from deceased female donor who died from heart failure. A 62-year-old women received a renal allograft in July 2006. Except for low-range proteinuria, renal function was normal until 6 months after transplantation when serum creatinine increased from 120 to 150 micromol/L. A renal biopsy was performed. Based on the specific pathological finding, AFD in donor was suspected. In order to prove the diagnosis, the other recipient also underwent renal biopsy 3 months later. This was 45-year-old female with stable graft function and nonnephrotic proteinuria. Light microscopic findings included a 'foamy' appearance of affected cells with swelling and vacuolization of podocytes. Electron microscopic finding show mesangial cells and podocytes filled with dense lysosomal granules appearing as myelin figures and 'zebra bodies'. Changes were less intensive than in the biopsy of the first recipient. The donor was 54-year-old Italian women who died on the Adriatic coast after heart attack. This is the first case of AFD found in a kidney allograft from deceased donor.
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PMID:Anderson-Fabry disease in kidneys from deceased donor. 1794 59

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