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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of bilateral neuroblastoma in the adrenal glands in a newborn led to the discovery of a family with clustering of tumors of neural crest origin. According to the two-mutation model of neuroblastoma development we searched for individuals with the first mutation, who are predisposed to neuroblastoma. Neither chromosomal analysis of the peripheral blood nor the examination of catecholamines nor of gm-phenotypes could mark the first step to neuroblastoma. However, it was possible to detect cystationinuria in familial neuroblastoma for the first time. Cystationinuria could be calssified as secondary to vitamin B6-deficiency. Since cystathioninuria and vitamin B6-deficiency were not only seen in blood-relations but also in relatives by marriage there was no fixed correlation to individuals with tumor or their relatives.
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PMID:[Genetic and biochemical studies on familial neuroblastoma]. 49 57

According to the two-mutation model of neuroblastoma several investigations were performed in order to find the gene carrier in a family with familial neuroblastoma. The results of these former studies are as follows: 1. Neither chromosomal analyses of the peripheral blood nor the examinations of catecholamines nor of cystathionine in the urine could mark the first step to neuroblastoma. 2. Since cystathioniuria was not only seen in blood-relations but also in relatives by marriage and since vitamin B6 deficiency was revealed, cystathioninuria was interpreted as secondary to vitamin B6 deficiency. In this study the normal values of cystathioninuria and vitamin B6 supply were examined. Furthermore the effect of oral vitamin B6 loading on cystathioninuria and oxaluria in familial neuroblastoma was investigated and the vitamin B6 supply in the neighbours of the family was analysed. The results permitted the following conclusions: 1. In 46 of 58 children and adults cystathioninuria was found in an immeasurable range by column chromatography. Only in 12 persons it could be measured quantitatively. With the exception of 6 explanable elevations no value exceeded 20 mumol/24 hr. These results show that the acceptance of the limiting value of 20 mumol/24 hr for increased cystathioninuria is justified. 2. Vitamine B6 deficiency was found in two of 7 patients. In one child this could be explained by the underlying disease. This finding supports the suggestion that vitamine B6 deficiency can relative frequently observed. 3. The examinations of cystathioninuria and oxaluria before and after loading with vitamine B6 showed different results. Whereas oxaluria decreased after loading cystathioninuria was not surely influenced. 4. The neighbours of the members with familial neuroblastoma showed mostly a reduced vitamine B6 supply. This fact could be an indication of exogenous reason of vitamine B6 deficiency in familial neuroblastoma.
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PMID:[Biochemical studies on familial neuroblastoma]. 64 89

In this study numerous amino acid analyses were performed in a family with increased incidence of tumors of the sympathetic nervous system. Since in 9 respectively 10 of a total of 13 surveyed persons an elevated urinary excretion of cystathionine was demonstrated with thin layer and column chromatographic methods, this constitutes the first report on cystathioninuria in familial neuroblastoma. Two family members also presented a homocystinuria in the spontaneously voided 24-hours urine. The only person whose plasma amino acids were analysed showed nearly normal levels. After oral loading with L-methionine the urinary excretion of cystathionine raised considerably. The different reaction of the two vitamin B6-dependent enzymes, cystathionine-synthetase and cystathionase, points at a different methionine induced sensitivity. The determination of pyridoxal phosphate and pyridoxal kinase detected a vitamin B6-deficiency, which corresponded well with an increased excretion of oxalic acid and a low normal urinary taurin excretion. Therefore these alterations of the amino acids are explained and thus urinary excretion of cystathionine can be interpreted as secondary cystathioninuria. Furthermore it was possible to provoke corresponding biochemical changes by oral administration of vitamin B6 such as reduction of the cystathioninuria and disappearance of the homocystinuria. In an infant the cystathioninuria could be observed over a period for 5 months, by which a transitory deficiency of the apoenzyme appears to be unlikely. The analysis of 24 hours urine samples of a gravida showed the persistance of cystathioninuria also during pregnancy. After radiation of a 5 year old girl with ganglioneuroblastoma an increase of the urinary cystathionine excretion and a first occurrence of homocystinuria was noted. These observations give rise to various considerations. The vitamin-B6-deficiency in familial neuroblastoma supports the assumption, that also the cystathioninuria in nonhereditary cases may be caused by vitamin-B6-deficiency. Since in this family the excretion of catecholamines was examined in a prior investigation a comparison of these two studies does not support the suggestion of a direct connection between the excretion of catecholamines and cystathioninuria, as it has been assumed to occur in sporadic neuroblastoma. The vitamin-B6-deficiency as seen in this family can also be considered in relation to tumor development. In the discussion about this possibility also the appearance of cystathioninuria in other tumors of early childhood is mentioned. Furthermore the relation of vitamin B6 to teratogenesis is commented on.
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PMID:[Secondary cystathioninuria due to vitamin B 6 deficiency in familial neuroblastoma]. 96 8

Cystathioninuria is a frequent and highly specific marker of neuroblastoma, but the etiology of this abnormality has not been well studied. To investigate this phenomenon, we analyzed 27 human neuroblastoma tissue specimens for the presence of cystathionine synthase and cystathionase. Levels of cystathionine synthase varied from undetectable to 622 pmol/mg protein, but no specimen had cystathionase measurable by rocket radioimmunoassay or catalytic assay. In addition, we assayed neuroblastoma cell lines exposed to a variety of differentiating agents: butyric acid, dimethyl sulfoxide, serum-free medium, or sodium citrate to induce differentiation. In each case we were unable to demonstrate cystathionase induction. These data are consistent with the hypothesis that neuroblastomas have a biochemical block in the transsulfuration enzymes at the level of cystathionase and that expression of cystathionine synthase in the absence of cystathionase may account for the presence of cystathioninuria in patients with neuroblastoma.
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PMID:Cystathionine metabolism in neuroblastoma. 338 29

Cystathionine is not normally present in urine and only a few cases of congenital cystathioninuria are known. Cystathioninuria has also been found in patients with sympathetic tumors or with primary hepatic tumors. This study was undertaken in order to assess the significance of cystathioninuria in the diagnosis and follow-up of patients with active neuroblastoma or ganglioneuroblastoma. It was found that 50% of these patients excrete cystathionine. The presence or severity of cystathioninuria does not correlate with the extent of metastases, nor is it combined with an elevated vanilmandelic acid excretion. By contrast, patients successfully treated for neuroblastoma, as well as patients with a variety of other tumors or diseases, do not show cystathioninuria. It is concluded that cystathioninuria is a valid test in the diagnosis of neuroblastoma or ganglioneuroblastoma, although primary liver tumors should be considered in the differential diagnosis. Furthermore, the presence of cystathioninuria in the follow-up course of these patients indicates that the neoplastic disease is still active.
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PMID:Cystathioninuria in patients with neuroblastoma or ganglioneuroblastoma. Its correlation to vanilmandelic acid excretion and its value in diagnosis and therapy. 521 8

Urinary excretion of cystathionine and dopa metabolites was analyzed in 61 patients with active neuroblastoma before, and at regular intervals during treatment. Thirty-seven patients with clinical evidence of active neuroblastoma excreted elevated levels of cystathionine before treatment was initiated; six other patients showed cystathioninuria at some time during treatment with chemo- or radiotherapy. The cause of the cystathioninuria remains unidentified. No relationship between excessive cystathionine excretion and liver impairment or liver metastases was established; nor was there evidence to support a consistent correlation with the ratio of the sum of the excretion values for vanilglycolic acid and vanilglycol to the excretion of vanilacetic acid. Our results indicate that absence of cystathioninuria correlates with an early clinical staging and thus with a favorable prognosis. Isolated cystathioninuria does occasionally occur in patients with neuroblastoma, permitting a presumptive diagnosis until later evidence can be obtained. Determination of cystathionine excretion is essential for an extensive biochemical evaluation of patients with neuroblastoma.
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PMID:Cystathioninuria in patients with neuroblastoma. 642 19

Isolation and identification of cystathionine were the basis for the determination of the renal cystathionine excretion in healthy children. Pathologically increased urinary levels of cystathionine may reflect either an inherited enzyme defect, or transient impaired adaptation in premature infants, or a secondary phenomenon in neuroblastoma and certain liver disorders. Pyridoxine dependency was shown in a child with primary cystathioninuria. Urinary cystathionine concentration in premature newborns decreased when treated with pyridoxine. Secondary cystathioninuria was found in biliary atresia, cytomegalovirus infection, neuroblastoma, vitamin D intoxication and hyperglycinemia.
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PMID:[Various forms of cystathioninuria]. 707 74