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)

Knowledge concerning SS (homozygous for the beta s gene) red blood cell (RBC) heterogeneity has been useful for understanding the pathophysiology of sickle cell anemia. No equivalent information exists for RBCs of the compound heterozygote for the beta s and beta c genes (SC) RBCs. These RBCs are known to be denser than most cells in normal blood and even most cells in SS blood (Fabry et al, J Clin Invest 70:1284, 1981). We have analyzed the characteristics of SC RBC heterogeneity and find that: (1) SC cells exhibit unusual morphologic features, particularly the tendency for membrane "folding" (multifolded, unifolded, and triangular shapes are all common); (2) SC RBCs containing crystals and some containing round hemoglobin (Hb) aggregates (billiard-ball cells) are detectable in circulating SC blood; (3) in contrast to normal reticulocytes, which are found mainly in a low-density RBC fraction, SC reticulocytes are found in the densest SC RBC fraction; and (4) both deoxygenation and replacement of extracellular Cl- by NO3- (both inhibitors of K:Cl cotransport) led to moderate depopulation of the dense fraction and a dramatic shift of the reticulocytes to lower density fractions. We conclude that the RBC heterogeneity of SC disease is very different from that of SS disease. The major contributions of properties introduced by HbC are "folded" RBCs, intracellular crystal formation in circulating SC cells, and apparently a very active K:Cl cotransporter that leads to unusually dense reticulocytes.
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PMID:The unique red cell heterogeneity of SC disease: crystal formation, dense reticulocytes, and unusual morphology. 191 87

Physicians must be able to recognize stroke caused by a mendelian or mitochondrial disorder. Some genetic disorders such as sickle cell anemia and Fabry disease have proven disease-specific treatments, whereas others have no effective treatment, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Proper diagnosis of a genetic disorder has prognostic value and prevents patient exposure to unnecessary and potentially harmful therapeutic agents and diagnostic tests. This article reviews the clinical and genetic features of some mendellan and mitochondrial disorders associated with ischemic stroke, hemorrhagic stroke, and cerebrovascular malformations.
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PMID:Genetics of cerebrovascular disorders. 1566 40

Persistent microscopic hematuria is present in about 6% of the population, but probably only a small minority have hematuria that does not originate from the glomerulus. Careful analysis of phase-contrast urine microscopy by a skilled observer is critically important in the investigation of hematuria. In glomerular disease, urine microscopy often is second only to renal biopsy examination in helping make a diagnosis. Glomerular and nonglomerular hematuria are distinguished easily on phase-contrast urine microscopy or by an automated peripheral blood cell counter. However, urine microscopy provides additional information about casts and other features that may enable such disparate diagnoses as Fabry's disease, sickle cell disease, and cystine calculi to be made. Macroscopic nonglomerular hematuria is of particular significance because it is much more likely than microscopic hematuria to be associated with malignancy. Macroscopic hematuria originating from the glomerulus indicates the presence of crescentic disease, which requires urgent assessment by renal biopsy examination. We advocate a renal biopsy examination in any individual with a persisting urinary erythrocyte count greater than 100,000/mL. Thirty percent of patients with isolated microscopic hematuria have mesangial immunoglobulin A glomerulonephritis (IgAN) shown on biopsy examination and 20% to 40% of these patients will progress to renal failure without treatment.
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PMID:The investigation of hematuria. 1588 Mar 21

Monogenic causes of stroke are rare but should not be missed by the neurologist. The purpose of this review is to aid the reader in the evaluation of a patient with cryptogenic stroke with or without a family history suspicious for an inherited condition. The clinical findings, diagnosis, and management of monogenic causes of stroke and stroke look-alikes are discussed, including cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry's disease, vascular Ehlers-Danlos, Marfan syndrome, sickle cell disease, the thrombophilias, hereditary hemorrhagic telangiectasia, cerebral cavernous malformations, hereditary cerebral hemorrhage with amyloidosis, and mitochondrial encephalopathy, lactic acidosis, and strokelike episodes. A quick review of systems designed to screen for genetic stroke causes is presented. By correlating stroke subtype with phenotype, this review will familiarize the clinician with indications for focused genetic testing in appropriate patients.
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PMID:Single-gene stroke disorders. 1647 42

Several hereditary disorders induce angiopathy in the intracranial cerebrovasculature and thus cause ischemic strokes. MELAS is a maternally inherited mitochondrial disorder that produces stroke-like events. Sickle cell disease, which is the result of a single base pair substitution, is a major cause of strokes in children. Homocystinuria, an autosomal recessive syndrome, produces premature atherosclerosis. Hereditary cerebroretinal vasculopathy is an autosomal dominant disorder that causes retinal and brain infarctions. Fabry disease is an x-linked disorder that can cause stroke in adults. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is an autosomal dominant syndrome that is associated with ischemic stroke and migraine-like headaches. The clinical presentation, stroke pathophysiology, and gene defects associated with these heritable disorders are reviewed.
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PMID:Mendelian and mitochondrial disorders associated with stroke. 1790 83

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7-8%, mainly due to primary glomerulonephritis (70-80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14-50% DR, 40-60% GL; atypical haemolytic uraemic syndrome 20-80% DR, 10-83% GL; membranoproliferative glomerulonephritis 30-100% DR, 17-61% GL; membranous nephropathy approximately 30% DR, approximately 50% GL; lipoprotein glomerulopathy approximately 100% DR and GL; primary hyperoxaluria type 1 80-100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36-60% DR, 7-10% GL; systemic lupus erythematosus 0-30% DR, 0-5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules.
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PMID:Disease recurrence in paediatric renal transplantation. 1924 94

Stroke is the third leading cause of death and a major cause of disability worldwide. Most cases of ischemic stroke are attributable to hypertension and other risk factors, but in over 20% of cases, the cause is unknown. Recent research has implicated some novel genes in the etiology of ischemic stroke, including genes for soluble epoxide hydrolase (sHE), 5-lipoxygenase activating protein (FLAP) and phosphodiesterase 4D (PDE4D). Moreover, thrombophilic states such as prothrombin G20210A mutation and factor V Leiden are now known to cause arterial stroke as well as venous thrombosis. Meanwhile, the recent availability of enzyme replacement therapy for Fabry disease and the proven benefits of regular blood transfusion in certain patients with sickle cell disease have greatly altered the outlook of these devastating inherited disorders. Thus, our understanding of the role of genetic factors in stroke raises the prospects for accurate assessment of future stroke risk among susceptible individuals, in whom early preventive measures may be life-saving. Further research into the genetics of stroke will clearly compliment ongoing national and international efforts to reduce the global burden of stroke.
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PMID:Genetics of ischemic stroke. 2106 58

Clinicians who treat patients with stroke need to be aware of several single-gene disorders that have ischemic stroke as a major feature, including sickle cell disease, Fabry disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and retinal vasculopathy with cerebral leukodystrophy. The reported genome-wide association studies of ischemic stroke and several related phenotypes (for example, ischemic white matter disease) have shown that no single common genetic variant imparts major risk. Larger studies with samples numbering in the thousands are ongoing to identify common variants with smaller effects on risk. Pharmacogenomic studies have uncovered genetic determinants of response to warfarin, statins and clopidogrel. Despite increasing knowledge of stroke genetics, incorporating this new knowledge into clinical practice remains a challenge. The goals of this article are to review common single-gene disorders relevant to ischemic stroke, summarize the status of candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors, and to briefly discuss pharmacogenomics related to stroke treatment.
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PMID:Genetic susceptibility to ischemic stroke. 2162 40