1/14. Elitek-rasburicase: an effective means to prevent and treat hyperuricemia associated with tumor lysis syndrome, a Meeting Report, Dallas, texas, January 2002.Renal precipitation of uric acid associated with tumor lysis syndrome (TLS) is a major complication in the management of leukemia, lymphoma, and other drug-sensitive cancers. Management of hyperuricema has historically consisted of administration of allopurinol, hydration, alkalinization to maintain pH between 7.0 and 7.3, and in some cases diuresis. allopurinol, a xanthine analogue, blocks xanthine oxidase and formation of uric acid. urate oxidase converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. Homo sapiens cannot express urate oxidase because of a nonsense mutation. urate oxidase was initially purified from aspergillus flavus fungus. Treatment with this nonrecombinant product had been effective in preventing renal precipitation of uric acid in cancer patients, but was associated with a relatively high frequency of allergic reactions. This enzyme was recently cloned from A. flavus and is now manufactured as a recombinant protein. Clinical trials have shown this drug to be more effective than allopurinol for prevention and treatment of hyperuricemia in leukemia and lymphoma patients. This drug has been approved in europe as well as the US and several clinical trials are in progress to further determine its clinical utility in other patient subsets. The purpose of this meeting was to discuss usefulness of recombinant urate oxidase, also known as rasburicase, Fasturtec, and Elitek, for the management of TLS in certain cancer patients.- - - - - - - - - - ranking = 1keywords = hyperuricemia (Clic here for more details about this article) |
2/14. Clinical characterization of a family with a mutation in the uromodulin (Tamm-Horsfall glycoprotein) gene.BACKGROUND: We have recently identified a mutation in the uromodulin gene in a large family affected with hyperuricemia, gout, and renal failure. The purpose of this investigation is to provide a comprehensive characterization of the clinical findings of this syndrome in family members who had a mutation in the uromodulin gene. methods: An extended family suffering from hyperuricemia and gout was identified by a local practitioner. After consent was obtained, patients provided a directed clinical history and blood and urine specimens for chemical and genetic testing. All family members were tested for the presence of uromodulin gene mutations by direct dna sequence analysis. The clinical and biochemical characteristics of family members carrying the affected mutation were then investigated. RESULTS: Thirty-nine family members were found to have an exon 5 uromodulin gene mutation (g.1966 1922 del), and 29 unaffected family members were identified. The cardinal clinical features in individuals with the uromodulin mutation included hyperuricemia, decreased fractional excretion of uric acid, and chronic interstitial renal disease leading to end-stage renal disease (ESRD) in the fifth through seventh decade. women did not always develop hyperuricemia or gout, but still developed progressive chronic renal failure. CONCLUSION: Mutation of the uromodulin gene resulted in hyperuricemia, reduced fractional excretion of uric acid, and renal failure. genetic testing will be required to definitively identify individuals suffering from this condition. We are interested in studying other families that may suffer from this condition and would appreciate any such referrals.- - - - - - - - - - ranking = 1keywords = hyperuricemia (Clic here for more details about this article) |
3/14. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman.Overactivity of phosphoribosylpyrophosphate synthetase (PRS) is an x chromosome-linked disorder of purine metabolism that is characterized by gout with uric acid overproduction and, in some families, neurodevelopmental impairment. We present the case of a 24-year-old Spanish woman with renal colic and hyperuricemia, which first manifested at age 11 years. Results of enzymatic and genetic studies supported the view that accelerated purine nucleotide and uric acid production in this woman resulted from defective allosteric regulation of PRS activity, which is, in turn, a consequence of a mutation in one of the patient's PRPS1 genes: an A-to-T substitution at nucleotide 578, encoding leucine for histidine at amino acid residue 192 of the mature PRS1 isoform. A previous example of disordered regulation of PRS1 activity in a family with a different substitution at the same amino acid residue strengthens this proposed mechanism. This is the first reported instance of PRS overactivity in which the propositus and sole affected family member is a woman.- - - - - - - - - - ranking = 0.2keywords = hyperuricemia (Clic here for more details about this article) |
4/14. Renal manifestations of a mutation in the uromodulin (Tamm Horsfall protein) gene.BACKGROUND: uromodulin (Tamm Horsfall glycoprotein) is the most abundant protein found in normal human urine. Its function has yet to be determined. Identifying mutations in the uromodulin gene may be helpful in understanding the function of uromodulin. There has been 1 report of 4 families suffering from mutations in the uromodulin gene, resulting in the autosomal dominant transmission of hypouricosuric hyperuricemia and chronic renal failure. This case report describes another family with similar clinical manifestations. methods: A family was identified with clinical characteristics of hypouricosuric hyperuricemia and renal failure occurring in a mother and daughter. Clinical characteristics were identified, and laboratory studies were obtained in the proband and the proband's daughter. A genetic analysis was performed to evaluate for mutations in the uromodulin gene. RESULTS: The proband suffered from hyperuricemia at an early age and progressive renal failure with end-stage renal disease developing at age 49 years. The proband's daughter suffered from hyperuricemia, a reduced fractional excretion of uric acid, and mild renal insufficiency. A g.2105G > A mutation in exon 4 of the uromodulin gene resulting in a substitution of tyrosine for cysteine was identified in both the proband and the proband's daughter. The clinical characteristics were similar to those of other patients suffering from uromodulin mutations and to those of patients suffering from medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy. CONCLUSION: uromodulin associated kidney disease results in hyperuricemia and renal failure. The specific uromodulin mutation found in this family is consistent with the hypothesis that mutations disrupt highly conserved cysteine residues in the uromodulin protein. Potential mechanisms for these pathologic changes are discussed. The authors would appreciate referral of other families for screening for mutations.- - - - - - - - - - ranking = 1keywords = hyperuricemia (Clic here for more details about this article) |
5/14. Associated giant cell tumor and tophaceous deposits in a finger pulp: a case report.A case of concomitant giant cell tumor of soft tissue and tophaceous deposits within the finger pulp is presented. The local hemorrhage and increased turnover with giant cell tumor may explain the deposits of aggregated crystals of monosodium urate in this patient with hyperuricemia.- - - - - - - - - - ranking = 0.2keywords = hyperuricemia (Clic here for more details about this article) |
6/14. Treatment of impending tumor lysis with single-dose rasburicase.OBJECTIVE: To report the experience of using rasburicase as a single-dose treatment for childhood leukemia presenting with hyperuricemia. CASE SUMMARIES: Three children with acute lymphoblastic leukemia presenting with hyperuricemia received rasburicase as a single intravenous dose just prior to the start of chemotherapy. This was followed by rapid reduction of serum uric acid levels within 24 hours, which remained low throughout induction therapy while allopurinol and hydration therapy without urinary alkalinization ensued. Subclinical tumor lysis was evidenced by the appearance of hyperphosphatemia and hypocalcemia in all cases and hyperkalemia in 1 patient. These abnormalities were transient, and each patient's renal function gradually improved from pretreatment baseline without requiring dialysis. DISCUSSION: Our experience suggests that hyperuricemia in children at risk for tumor lysis can be managed with a briefer regimen of rasburicase than the recommended 5- to 7-day course. CONCLUSIONS: A shorter course of rasburicase treatment, including single-dose injection, is feasible and will improve the cost-effectiveness profile of the otherwise expensive compound.- - - - - - - - - - ranking = 0.6keywords = hyperuricemia (Clic here for more details about this article) |
7/14. Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient.A 29-year-old woman was referred to our department because of gout. Routine laboratory data showed hyperuricemia, a high level of plasma oxypurines, increased urinary uric acid excretion, and increased urinary oxypurine excretion, with decreased hypoxanthine phosphoribosyl transferase (HPRT) activity in the erythrocytes. From these findings, the patient was diagnosed with a partial deficiency of HPRT. To determine its properties, a cDNA sequence encoding HPRT and the androgen receptor AR XIST minimal promoter gene, as well as methylation of the AR gene were investigated. The HPRT cDNA sequence revealed a point mutation of G to A in nucleotide 40, which changed codon 14 from GAA (Glu) to AAA (Lys) in the mutant gene. In addition, the HPRT genomic dna sequence, including the mutation site, revealed the same point mutation, indicating that the patient was heterozygote. Further analysis of the AR gene on the x chromosome suggested nonrandom X-chromosome inactivation, whereas the AR XIST minimal promoter gene was normal. Such results have not been previously reported in a female with partial HPRT deficiency.- - - - - - - - - - ranking = 1keywords = hyperuricemia (Clic here for more details about this article) |
8/14. hyperuricemia and reticulocytopenia in association with autoimmune hemolytic anemia in two children.hyperuricemia developed in 2 children with autoimmune hemolytic anemia with reticulocytopenia at a time of hemolytic crisis. One likely cause of hyperuricemia is the destruction of nucleated RBC precursors by autoantibodies. It is advised that patients with autoimmune hemolytic anemia with reticulocytopenia be examined for hyperuricemia. This might explain the reason for reticulocytopenia and might prevent unnecessary bone marrow procedures. When hyperuricemia is present, supportive therapy might be needed to prevent renal damage.- - - - - - - - - - ranking = 0.6keywords = hyperuricemia (Clic here for more details about this article) |
9/14. Acute renal failure due to tumor lysis syndrome in a patient with non-Hodgkin's lymphoma.tumor lysis syndrome is characterized by multiple metabolic derangements resulting from the release of intracellular components into the bloodstream due to abrupt malignant cell death, spontaneously or following antineoplastic therapy. The syndrome is characterized by hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia, while deposition of uric acid and calcium phosphate crystals may result in acute renal failure, which is often exacerbated by concomitant intravascular volume depletion. A case of tumor lysis syndrome complicated by acute renal failure in a patient with non-Hodgkin's lymphoma is reported and the pathophysiology, the clinical features, and the treatment options are discussed.- - - - - - - - - - ranking = 0.2keywords = hyperuricemia (Clic here for more details about this article) |
10/14. A novel heterozygous missense mutation in the UMOD gene responsible for Familial Juvenile Hyperuricemic Nephropathy.BACKGROUND: Familial Juvenile Hyperuricemic Nephropathy is an autosomal dominant nephropathy, characterized by decreased urate excretion and progressive interstitial nephritis. Mutations in the uromodulin coding UMOD gene have been found responsible for the disease in some families. CASE PRESENTATION: We here describe a novel heterozygous p.K307T mutation in an affected female with hyperuricemia, renal cysts and renal failure. The proband's only son is also affected and the mutation was found to segregate with the disease. CONCLUSIONS: This mutation is the fourth reported in exon 5. Initial studies identified a mutation clustering in exon 4 and it has been recommended that sequencing this exon alone should be the first diagnostic test in patients with chronic interstitial nephritis with gout or hyperuricemia. However, regarding the increasing number of mutations being reported in exon 5, we now suggest that sequencing exon 5 should also be performed.- - - - - - - - - - ranking = 0.4keywords = hyperuricemia (Clic here for more details about this article) |
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