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)

The results of kidney transplantation in a variety of renal diseases have been analyzed. The diseases causing end-stage kidney failure in recipients were Alport syndrome, amyloidosis, cystinosis, diabetes mellitus, Fabry disease, familial nephritis, gout, medullary cystic disease, oxalosis, and systemic lupus erythematosus. The data indicate that renal transplantation is justifiable and parallels functional results for the more common causes of end-stage renal disease in all but Fabry disease and oxalosis. Although Fabry disease did not recur in any grafted kidney, only three patients have a functioning graft one year after transplantation. From a group of ten patients with oxalosis who received a total of 14 kidneys, only one survives. In no other metabolic disease, except one instance of primary amyloidosis, did the metabolic disease notably affect the transplant as it did in oxalosis.
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PMID:Renal transplantation in congenital and metabolic diseases. A report from the ASC/NIH renal transplant registry. 80 49

Methods for the PCR amplification of five polymorphic sites in the region Xq21.33 to Xq24 were developed and used to predict heterozygosity for Fabry disease in informative families. Clones containing polymorphic sites associated with DNA segments DXS17, DXS87, and DXS287, and the alpha-galactosidase A gene were isolated from genomic libraries. Surrounding nucleotide sequences and optimal conditions for amplification of each polymorphic site were determined. These amplifiable polymorphisms provided predictions of heterozygosity for Fabry disease and should be useful for diagnostic linkage analyses in Alport syndrome, X-linked cleft palate and ankyloglossia, Pelizaeus-Merzbacher disease, and X-linked agammaglobulinemia as well as sequence-tagged sites for gene mapping.
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PMID:Amplification of human polymorphic sites in the X-chromosomal region q21.33 to q24: DXS17, DXS87, DXS287, and alpha-galactosidase A. 134 83

Little information is available concerning hereditary renal disease in the Irish population. We studied the prevalence and types of hereditary renal disease that lead to end stage renal failure by looking at the underlying hereditary disease in our dialysis populations and in all patients transplanted at the national unit. Twenty eight (15.7%) of 178 dialysis patients had hereditary renal disease with a mean age of 31 years (range nine to 65), and a male to female ratio of 1.54:1. Eighty-nine of 842 patients (10.3%) with renal transplants had hereditary renal disease with a male to female ratio of 1.63:1. The commonest entity was autosomal dominant polycystic kidney disease (68% in dialysis patients, 64% in transplants), and the next most frequent was Alport's syndrome (21.4%, 16.9%). Nephronophthisis was the third most common problem (10.7%, 10.1%) followed by hereditary non-Alport's nephritis, Fabry's disease, cystinosis and familial interstitial nephritis. The high prevalence of hereditary renal disease among the dialysis and renal transplant population emphasises the need for proper registration of the nature of renal disease in this group, and for a comprehensive genetic counselling service in this country.
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PMID:Prevalence of hereditary renal disease. 236 28

Several disease loci have been mapped to the Xq21.3-Xq22 region of the human X Chromosome (Chr) including X-linked agammaglobulinemia (XLA), Fabry disease, Alport syndrome, and Pelizaeus Merzbacher disease. Upon cloning of the XLA gene, Bruton's tyrosine kinase (btk), both Fabry disease and XLA were mapped within the same 50- to 70-kb interval. In order to investigate the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk. Two of these cosmids spanning most of the coding sequence and the upstream region of btk and gla, U237D10 and U230D1, were sequenced by a random shotgun strategy combined with automated sequencing, resulting in 69 kb of contiguous genomic sequence. Sequencing of U237D10 showed btk to be comprised of 19 exons spanning over 35 kb. Sequencing of U230D1 showed that the 3' end of gla is 9 kb from the 5' end of btk and also demonstrated the presence of two additional genes in the region immediately 5' to btk. The surprisingly high gene density is similar to that seen previously only in the human major histocompatibility locus.
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PMID:Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci. 762 84

Virtually all diseases affecting the native kidney recur in the kidney transplant with the exception of Alport syndrome, polycystic kidney disease, hypertension, chronic pyelonephritis, and chronic interstitial nephritis. Fortunately, in the majority of patients, recurrence of the original disease has minimal clinical impact, with only approximately 5% of all graft loss occurring as a result of recurrent disease. The primary renal diseases that commonly recur include membranoproliferative glomerulonephritis type II, IgA nephropathy, and focal and segmental glomerular sclerosis. The most common systemic disease that recurs is diabetic nephropathy. Living-related transplantation should be used with caution in patients with the hemolytic uremic syndrome, recurrent focal and segmental glomerular sclerosis, and membraneous glomerulonephritis. Fabry disease and primary hyperoxaluria type I are no longer absolute contraindications to kidney transplantation.
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PMID:Recurrent diseases in the kidney transplant. 802 19

The introduction of molecular therapy through the delivery of nucleic acids either as oligonucleotides or genetic constructs holds enormous promise for the treatment of renal disease. Significant barriers remain, however, before successful organ-specific molecular therapy can be applied to the kidney. These include the development of methods to target the kidney selectively, the definition of vectors that transduce renal tissue, the identification of appropriate molecular targets, the development of constructs that are regulated and expressed for long periods of time, the demonstration of efficacy in vivo, and the demonstration of safety in humans. As the genetic and pathophysiologic basis of renal disease is clarified, obvious targets for therapy will be defined, for example, polycystin in polycystic kidney disease, human immunodeficiency virus (HIV) type 1 in HIV-associated nephropathy, alpha-galactosidase A in Fabry's disease, insulin in diabetic nephropathy, and the "minor" collagen IV chains in Alport's syndrome. In addition, several potential mediators of progressive renal disease may be amenable to molecular therapeutic strategies, such as interleukin-6, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta(TGF-beta). To test the in vivo efficacy of molecular therapy, appropriate animal models for these disease states must be developed, an area that has received too little attention. For the successful delivery of genetic constructs to the kidney, both viral and nonviral vector systems will be required. The kidney has a major advantage over other solid organs since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the uroexcretory pathways, and ex vivo during transplantation. To further restrict expression to the kidney, tropic vectors and tissue-specific promoters also must be developed. For the purpose of inhibition of endogenous or exogenous genes, current therapeutic modalities include the delivery of antisense oligodeoxynucleotides or ribozymes. For these approaches to succeed, we must gain a much better understanding of the nature of their transport into the kidney, requirements for specificity, and in vivo mechanisms of action. The danger of a rush to clinical application is that superficial approaches to these issues will likely fail and enthusiasm will be lost for an area that should be one of the most exciting developments in therapeutics in the next decade.
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PMID:Molecular therapy for renal diseases. 884 Sep 36

Inherited kidney diseases are frequently encountered in adults; the diagnosis is often made and they usually progress to renal failure at this age. Autosomal dominant polycystic kidney disease is the most prevalent. It is one of the most common inherited diseases, involving 1 in 400 to 1,000 individuals. Renal cysts growth is responsible for hypertension and renal failure; polycystic kidney disease represents 6 to 7% of the causes of end-stage renal failure in adults. The disease also encompasses extra-renal localisations, i.e. liver cysts and intra-cranial aneurysms. Multiple renal cysts may be found in other inherited disorders, such as tuberons sclerosis and von Hippel-Lindau disease. Alport syndrome is the second most prevalent inherited kidney disease, characterized by various abnormalities of type IV collagen molecules. Molecular diagnosis is possible in some families, which makes genetic counselling more reliable. Finally renal involvement is frequent in a great variety of inherited metabolic (Fabry's disease, glycogen storage disease type 1, hyperuricemic nephropathy) or non-metabolic (nail-patella or Bardet-Biedl syndrome) diseases.
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PMID:[Hereditary kidney diseases in adults]. 936 16

Hereditary diseases have to be considered in the differential diagnosis of many kidney diseases. The kidney can be affected by systemic metabolic diseases such as primary hyperoxaluria or Fabry's disease. Inborn errors of the coagulation cascade or the complement system may cause familiar forms of the hemolytic uremic syndrome. Of central interest are hereditary cystic kidney diseases with autosomal dominant polycystic kidney disease as its most prominent example. Hereditary forms of the nephrotic syndrome are usually caused by abnormalities of podocyte function. Alport's syndrome is a classical example of a basement membrane disease. Of special interest are hereditary defects in tubular transport mechanisms such as carrier defects affecting sodium reabsorption along the tubulus.
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PMID:[Pathogenesis and clinical course of hereditary nephropathies]. 1147 6

Clinical genetics has reached a crossroads. Indeed recent progress in molecular genetics has generated great hope. This progress has consequences beyond genetic diseases, leading to the understanding of much more general mechanisms of disease. This progress has also permitted a better classification of genetic entities, such as Alport's syndrome, based on the molecular mechanisms involved. Lastly this progress allows us to design pharmacologic therapeutic approaches. Enzyme replacement therapy in Fabry's disease is a recent example of this approach. Difficulties are much greater in diseases such as autosomal dominant polycystic kidney disease. To reach these goals, height collaboration between molecular genetics and cell biology in the post-gene era, and between clinical genetics and other medical specialties, is required not only in the field of pediatric diseases, but also in late-onset genetic diseases.
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PMID:[Clinical genetics at the crossroads: the example of hereditary kidney diseases]. 1237 Dec 69

To establish the role of electron microscopy in the diagnosis of glomerular diseases we reviewed retrospectively 113 renal biopsies. The biopsies were included in this study if tissue was received for light microscopy, immunofluorescence and electron microscopy. The biopsy was assigned to one of the three following categories on the contribution of the ultrastructural findings to the primary diagnosis: essential, important, and not required. Our study revealed that electron microscopy was essential to establish the primary diagnosis in 35 cases (31.0%), was important, but did not alter the preliminary diagnosis in 15 cases (13.3%) and in 63 cases (55.7%) the ultrastructural examination was not needed to confirm the diagnosis. Electron microscopy was essential to create diagnosis in a total of two cases of thin basement membrane disease, in nephropathy in Alport syndrome, in nephropathy in Fabry disease, and was necessary for establishing final diagnosis in 12 cases (85.7%) of minimal lesion. On the basis of electron microscopy it was also possible to establish the precise diagnosis of subtypes in mesangiocapillary glomerulonephritides, describe the stage of membranous glomerulopathy, and find thickening of glomerular basement membrane in the pre-diabetic state. Moreover, ultrastructural examination was helpful to differentiate membranous and mesangiocapillary glomerulonephritis, minimal change nephropathy and early membranous lesions, and distinguish membranous lupus nephritis from idiopathic membranous nephropathy The electron microscopy findings were not of any help in establishing the diagnosis and did not obtain any valuable information in all cases of amyloid nephropathy and IgA nephropathy, as well as in the majority of focal segmental glomerulosclerosis, extracapillary glomerulonephritides, and mesangial proliferative glomerulopathies. In conclusion, the results showed that in 44.3% of glomerulopathies the ultrastructural study provides fundamental or important diagnostic information, and therefore electron microscopy still remains a useful tool in the diagnosis of glomerular diseases.
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PMID:Current position of electron microscopy in the diagnosis of glomerular diseases. 1771 74


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