Journal of pediatric biochemistry最新文献_第10页

Management of urea cycle defects in a developing country 发展中国家尿素循环缺陷的管理

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586456

A. Jalan, K. Kudalkar, R. Jalan

{"title":"Management of urea cycle defects in a developing country","authors":"A. Jalan, K. Kudalkar, R. Jalan","doi":"10.1055/s-0036-1586456","DOIUrl":"https://doi.org/10.1055/s-0036-1586456","url":null,"abstract":"Abstract Urea cycle disorders (UCDs) are amongst the commonest disorders detected in critically ill newborns. True incidence of these disorders in developing countries like India may not be known, however they are expected to be very common owing to the high rate of consanguinity in these countries. In this review article we discuss the problems and hardships faced by treating clinicians in a developing country. We present an overview of the strategies to be followed by clinicians in a developing country for treatment and management of such disorders. Management of disorders like UCDs in a developing country has many complexities and limitations. The outcome in these disorders depends upon many factors like availability of basic investigations, availability of emergency drugs, availability of special diets and their cost-effectiveness. Alternative methods for ammonia detoxification like peritoneal dialysis and hemodialysis may or may not be available at all the centers managing critically ill newborns with UCDs, which may in turn affect the outcome in these children. Liver transplants are rarely available. Thus increasing the awareness about these disorders and educating the primary physicians in treatment and management of such disorders become an essential part in the management of these disorders. Emergency protocols to be followed during treatment have been described in this review.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"43 7 1","pages":"011 - 016"},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58159923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disorders leading to an impairment of the urea cycle and hyperammonemia 导致尿素循环障碍和高氨血症的疾病

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586460

D. Martinelli

引用次数: 0

Urea cycle disorders revisited – clinical, biochemical and therapeutical aspects 重新审视尿素循环障碍-临床，生化和治疗方面

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586454

J. Häberle

引用次数: 2

Stable isotopes in the diagnosis and treatment of inherited hyperammonemia 稳定同位素在遗传性高氨血症诊断和治疗中的应用

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586461

N. Ah Mew, M. Yudkoff, M. Tuchman

引用次数: 12

Challenges of experimental gene therapy for urea cycle disorders 尿素循环障碍实验基因治疗的挑战

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586462

H. Viecelli, B. Thöny

{"title":"Challenges of experimental gene therapy for urea cycle disorders","authors":"H. Viecelli, B. Thöny","doi":"10.1055/s-0036-1586462","DOIUrl":"https://doi.org/10.1055/s-0036-1586462","url":null,"abstract":"Abstract Urea cycle disorders (UCDs) are inborn errors of liver metabolism that often result in hyperammonemia and failure of arginine synthesis due to the deficiencies of one of the six enzymes or two mitochondrial transporters involved. Despite current treatment options, including dietary therapy, stimulation of alternative routes of nitrogen disposal and cell therapies (hepatocyte and orthotopic liver transplantation), significant morbidity and mortality still remain. Gene therapy has emerged as an attractive alternative strategy for providing a definitive cure for patients with metabolic diseases. Successful phenotype correction in pre-clinical animal models is encouraging and research effort is increasingly being focused on translation from the laboratory bench to proof-of-concept human therapy. Gene therapy for UCDs must target the periportal hepatocytes, as these are the only liver cells that express all six enzymes required for full ammonia detoxification. This review explores current efforts to develop and translate liver-directed gene therapy approaches to UCDs caused by each of the defects of the six enzymes. The prominent issues that will need to be addressed and overcome for the future development of clinical trials, including alternatives to mouse mutants and to vectors that are not necessarily conditioned to rodents are also discussed.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"04 1","pages":"065 - 073"},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1586462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58159531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Variability of OTC deficiency in heterozygous carriers: Case report of a family 杂合子携带者OTC缺乏的变异性：一个家族的病例报告

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586455

C. Staufner, K. Zangerl, G. Hoffmann, S. Kölker

引用次数: 0

Current role of enzyme analysis for urea cycle disorders 酶分析在尿素循环紊乱中的作用

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586458

M. Gautschi, S. Eggimann, J. Nuoffer

引用次数: 6

Mutation analysis of urea cycle disorders 尿素循环紊乱的突变分析

Journal of pediatric biochemistry Pub Date : 2014-03-01 DOI: 10.1055/s-0036-1586459

V. Rüfenacht, J. Häberle

{"title":"Mutation analysis of urea cycle disorders","authors":"V. Rüfenacht, J. Häberle","doi":"10.1055/s-0036-1586459","DOIUrl":"https://doi.org/10.1055/s-0036-1586459","url":null,"abstract":"Abstract Urea cycle disorders (UCDs) are a group of autosomal or X-linked, recessively inherited errors of metabolism that lead to severe neurological disease due to insufficient detoxification of excess nitrogen. The resulting hyperammonemia is the key feature of UCDs, but at the same time only a surrogate marker. In the majority of cases, a sole biochemical analysis is indicative but not diagnostic. Therefore, additional means are required and mutation analysis is the method of choice for confirmation in most cases of UCD. In addition to confirming the diagnosis, mutation analysis enables genetic counseling and prenatal testing and contributes to new research approaches. All genes involved in any of the enzymatic (namely the genes for N-acetylglutamate synthase, NAGS; carbamoylphosphate synthetase, CPS1; ornithine transcarbamylase, OTC; argininosuccinate synthetase, ASS1; argininosuccinate lyase, ASL; arginase, ARG1) or transporter steps (namely the genes for the ornithine/citrulline antiporter ORNT1, SLC25A15; glutamate/aspartate antiporter citrin, SLC25A13) of the urea cycle are known and thus accessible for genetic testing. In most situations, direct Sanger sequencing using DNA from peripheral blood cells can be done but there are exceptions to this such as in the case of the relatively large CPS1 gene which renders RNA based mutation analysis an attractive alternative. With this review, we provide an overview on the current methods used for mutation analysis of each UCD gene, we mention possible pitfalls and their solutions, and discuss alternative methods which may become standard in the future.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"04 1","pages":"033 - 043"},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58159991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Stable isotopes in the diagnosis and treatment of inherited hyperammonemia. 稳定同位素在遗传性高氨血症诊断和治疗中的应用。

Journal of pediatric biochemistry Pub Date : 2014-01-01 DOI: 10.3233/JPB-140106

Nicholas Ah Mew, Marc Yudkoff, Mendel Tuchman

引用次数: 0

Systematic review of large neutral amino acids for treatment of phenylketonuria 大中性氨基酸治疗苯丙酮尿的系统综述

Journal of pediatric biochemistry Pub Date : 2013-12-01 DOI: 10.1055/s-0036-1586446

M. Lindegren, S. Krishnaswami, T. Reimschisel, C. Fonnesbeck, Nila A. Sathe, M. McPheeters

{"title":"Systematic review of large neutral amino acids for treatment of phenylketonuria","authors":"M. Lindegren, S. Krishnaswami, T. Reimschisel, C. Fonnesbeck, Nila A. Sathe, M. McPheeters","doi":"10.1055/s-0036-1586446","DOIUrl":"https://doi.org/10.1055/s-0036-1586446","url":null,"abstract":"Abstract Individuals with phenylketonuria (PKU) have defective enzyme activity, leading to toxic accumulation of phenylalanine (Phe) in blood and tissues. Adherence to a Phe-restricted diet can mitigate poor outcomes; however, dietary restriction is difficult. Large neutral amino acids (LNAAs), which putatively decrease brain Phe concentration, have been suggested as a potential supplementary treatment in addition to a Phe-restricted diet. To systematically review evidence regarding LNAA usage in individuals with PKU, we searched 5 databases including Medline up to August 2011 and the reference lists of included articles. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics and outcomes; using their extracted data, they assigned overall quality and strength of evidence ratings based on predetermined criteria. Three small studies (two randomized controlled trials and one uncontrolled open label trial) of fair to poor quality investigated LNAAs. The studies included a total of 47 participants with severe PKU between 11 and 45 years of age receiving LNAAs for 1 to 8 weeks. In all three studies, blood Phe decreased after one week of treatment, but remained above clinically acceptable levels. The one trial measuring correlation between blood and brain Phe found no association. Research on adjuvant therapy in PKU to complement dietary restriction is early in its development and substantially more work is needed. The three very small studies of LNAAs to date cannot be considered as more than proof of concept.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"03 1","pages":"181 - 186"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1586446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58159738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1