Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent attempts to detect mutations involving single base changes or small deletions that are specific to genetic diseases provide an opportunity to develop a two-tier mutation-screening program through which incidence of rare genetic disorders and gene carriers may be precisely estimated. A two-tier survey consists of mutation screening in a sample of patients with specific genetic disorders and in a second sample of newborns from the same population in which mutation frequency is evaluated. We provide the statistical basis for evaluating the incidence of affected and gene carriers in such two-tier mutation-screening surveys, from which the precision of the estimates is derived. Sample-size requirements of such two-tier mutation-screening surveys are evaluated. Considering examples of cystic fibrosis (CF) and medium-chain acyl-CoA dehydrogenase deficiency (MCAD), the two most frequent autosomal recessive disease in Caucasian populations and the two most frequent mutations (delta F508 and G985) that occur on these disease allele-bearing chromosomes, we show that, with 50-100 patients and a 20-fold larger sample of newborns screened for these mutations, the incidence of such diseases and their gene carriers in a population may be quite reliably estimated. The theory developed here is also applicable to rare autosomal dominant diseases for which disease-specific mutations are found.
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PMID:Estimation of the incidence of a rare genetic disease through a two-tier mutation survey. 850 45

Investigations of genetic diseases such as cystic fibrosis, alpha-1-antitrypsin deficiency, phenylketonuria, mitochondrial acyl-CoA dehydrogenase deficiencies, and many others have shown that enhanced proteolytic degradation of mutant proteins is a common molecular pathological mechanism. Detailed studies of the fate of mutant proteins in some of these diseases have revealed that impaired or aberrant folding of mutant polypeptides typically results in prolonged interaction with molecular chaperones and degradation by intracellular proteases before the functional conformation is acquired. This appears to be the case for many missense mutations and short in-frame deletions or insertions that represent a major fraction of the mutations detected in genetic diseases. In some diseases, or under some circumstances, the degradation system is not efficient. Instead, aberrant folding leads to accumulation of protein aggregates that damage the cell. Mechanisms by which misfolded proteins are selected for degradation have first been delineated for the endoplasmatic reticulum; this process has been termed "protein quality control." Similar mechanisms appear to be operative in all cellular compartments in which proteins fold. Within the context of genetic diseases, we review knowledge on the molecular processes underlying protein quality control in the various subcellular compartments. The important impact of such systems for variability of the expression of genetic deficiencies is emphasised.
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PMID:Protein misfolding and degradation in genetic diseases. 1047 27

Advances in technology provide new challenges to public health to implement screening programs that are effective, cost-efficient, and available to all infants regardless of ability to pay. The Newborn Metabolic Disorder Screening Program (NMDSP) of the Oklahoma State Department of Health is evaluating the expansion of newborn screening for the disorders of cystic fibrosis, congenital adrenal hyperplasia, and medium-chain acyl coenzyme A dehydrogenase deficiency (MCAD) to the current screening battery of disorders (phenylketonuria, congenital hypothyroidism, galactosemia, and sickle cell disease). The challenge is to offer these new screening tests in a cost-efficient manner that ensures all newborns have access to screening and that an infrastructure exists to diagnose and provide the specialized comprehensive care affected infants will require to reduce the morbidity, mortality, and disability associated with these disorders. Essential components of an effective newborn screening system include the smooth integration of sample collection, laboratory testing, follow-up, diagnosis, timely treatment, and tracking components. The NMDSP has recommended that screening should be expanded, but issues of cost and the establishment of a sustainable infrastructure of comprehensive medical services must be addressed.
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PMID:Public health explores expanding newborn screening for cystic fibrosis, congenital adrenal hyperplasia, and medium-chain acyl coenzyme A dehydrogenase deficiency (MCAD). 1139 80

The Health Council of the Netherlands has published an advisory report on neonatal screening in view of developments in diagnostics, therapy and the prevalence of neonatal diseases. Currently it involves screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia. Because screening may lead to considerably better outcomes in affected newborns, the council recommends expanding current screening to include medium-chain acyl-CoA dehydrogenase deficiency, sickle-cell disease and 12 other rare disorders: biotinidase deficiency, galactosaemia, glutaricaciduria type I, HMG-CoA lyase deficiency, holocarboxylase-synthetase deficiency, homocystinuria, isovaleric-acidaemia, long-chain hydroxyacyl-CoA dehydrogenase deficiency, maple syrup urine disease, 3-methylcrotonyl-CoA carboxylase deficiency, tyrosinaemia I and very-long-chain acyl-CoA dehydrogenase deficiency. A better detection method for cystic fibrosis must be developed before it is included in screening to restrict the number of sweat-test referrals of unaffected newborns. The council recommends providing information on neonatal screening during pregnancy and gives special attention to the possibility of detecting carriership in the parents.
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PMID:[The advisory report 'Neonatal screening' from the Health Council of The Netherlands]. 1639 64

Newborn screening (NBS)--in which each newborn infant is screened for up to 50 specific metabolic disorders for early detection and intervention--is the first program of populationwide genetic testing. As a public health intervention, NBS has greatly improved the lives of thousands of affected children. New technologies and new economic and social forces pose significant ethical and clinical challenges to NBS. Two primary challenges concern (1) accommodating clinical and ethical standards to rapid technological developments in NBS and (2) preparing public health systems to respond to the medical advances and social forces driving expansion of NBS programs. We describe and analyze these challenges through consideration of 3 disorders: phenylketonuria, medium-chain acyl-CoA dehydrogenase deficiency, and cystic fibrosis.
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PMID:Newborn screening: complexities in universal genetic testing. 1732 34

Newborn screening fact sheets were last revised in 1996 by the American Academy of Pediatrics Committee on Genetics. This revision was prompted by advances in the field since 1996, including technologic innovations, as well as greater appreciation of ethical issues such as those surrounding informed consent. The following disorders are discussed in this revision of the newborn screening fact sheets: biotinidase deficiency, congenital adrenal hyperplasia, congenital hearing loss, congenital hypothyroidism, cystic fibrosis, galactosemia, homocystinuria, maple syrup urine disease, medium-chain acyl-coenzyme A dehydrogenase deficiency, phenylketonuria, sickle cell disease and other hemoglobinopathies, and tyrosinemia. A series of topics related to newborn screening is discussed in a companion publication to this electronic publication of the fact sheets (available at: www.pediatrics.org/cgi/content/full/118/3/1304). These topics are newborn screening as a public health system; factors contributing to the need for review of the newborn screening system; informed consent; tandem mass spectrometry; DNA analysis in newborn screening; status of newborn screening in the United States; and the effect of sample timing, preterm birth, diet, transfusion, and total parenteral nutrition on newborn screening results.
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PMID:Newborn screening fact sheets. 1695 Sep 73

Newborn screening fact sheets were last revised in 1996 by the Committee on Genetics of the American Academy of Pediatrics. These fact sheets have been revised again because of advances in the field, including technologic innovations such as tandem mass spectrometry, as well as greater appreciation of ethical issues such as informed consent. The fact sheets provide information to assist pediatricians and other professionals who care for children in performing their essential role within the newborn screening public health system. The newborn screening system consists of 5 parts: (1) newborn testing; (2) follow-up of abnormal screening results to facilitate timely diagnostic testing and management; (3) diagnostic testing; (4) disease management, which requires coordination with the medical home and genetic counseling; and (5) continuous evaluation and improvement of the newborn screening system. The following disorders are reviewed in the newborn screening fact sheets (which are available at www.pediatrics.org/cgi/content/full/118/3/e934): biotinidase deficiency, congenital adrenal hyperplasia, congenital hearing loss, congenital hypothyroidism, cystic fibrosis, galactosemia,homocystinuria, maple syrup urine disease, medium-chain acyl-coenzyme A dehydrogenase deficiency, phenylketonuria, sickle cell disease and other hemoglobinopathies,and tyrosinemia.
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PMID:Introduction to the newborn screening fact sheets. 1696 Sep 84

This report outlines the status of neonatal screening in Europe in 2004. Out of the 45 member states of the Council of Europe plus the regions Scotland and Wales (in total 47 'countries'), no data at all were available from 3 (Albania, Azerbaijan and Georgia). From the other 44, varying amounts of data were received. Apart from Armenia, Finland and Malta, all countries have a national programme for phenylketonuria (PKU), although in some countries those programmes do not yet have 100% coverage. Moldova and Ukraine have no national programme for congenital hypothyroidism (CH), the other countries do. Twelve countries screen for congenital adrenal hyperplasia (CAH), 6 for cystic fibrosis (CF) and 7 for galactosaemia (GAL), 6 for biotinidase deficiency (BD) and 4 for medium-chain acyl-CoA dehydrogenase deficiency (MCAD). Some countries have pilot programmes for certain conditions or different programmes per screening laboratory. The prevalences for PKU vary from 1:3000 to 1:30,000, and for CH from 1:1300 to 1:13,000. Methodologies vary within and between countries. There appears to be no relationship between the cut-off limits and the recall rate. A first priority is to help those countries where the basic screening programmes have less than 100% coverage. In addition, continuous monitoring of the European programmes will help to decrease the variation in design and methodology by making use of the knowledge and expertise available from the global membership of the International Society for Neonatal Screening (ISNS). The huge difference of recall rates illustrate one obvious and important area for improvement of programme performances that could be aided by strengthened European cooperation.
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PMID:Neonatal screening in Europe; the situation in 2004. 1761 47

In 2005, a federal advisory committee recommended that the number of disorders in state newborn screening programs be expanded from 9 to 29. In view of this recommendation, state leaders will need to make cogent decisions regarding the expanse of their state newborn screening programs. They must consider several factors, including the costs and outcomes of the screening program. The expense of the initial screening test can be misleading because it does not include the cost of the entire program (testing, tracking, notifying, retesting, confirmatory testing, and follow-up). Also, outcomes such as false positive findings can be costly to newborn screening programs, result in additional testing for infants, and lead to parental concern and worry. This article examines some of the policy issues related to newborn screening and specifically focuses on three disorders recommended for newborn screening, cystic fibrosis (CF), medium-chain acyl CoA dehydrogenase Deficiency (MCADD), and beta-ketothiolase (BKT).
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PMID:Policy issues related to expanded newborn screening: a review of three genetic/metabolic disorders. 1817 27

The aim of newborn screening is to detect newborns with serious, treatable disorders so as to facilitate appropriate interventions to avoid or ameliorate adverse outcomes. Mass biochemical testing of newborn babies was pioneered in the 1960s with the introduction of screening for phenylketonuria, a rare inborn error of metabolism, tested by using a dried blood spot sample. The next disorder introduced into screening programs was congenital hypothyroidism and a few more much rarer disorders were gradually included. Two recent advances have greatly changed the pace: modification of tandem mass spectrometry and DNA extraction and analysis from newborn screening dried blood spot. These two technologies make the future possibilities of newborn screening seem almost unlimited. Newborn screening tests are usually carried out on a dried blood spot sample, for which there are special analytical considerations. Dried blood spot calibrators and controls, prepared on the same lot number of filter paper, are needed. Methods have a co-efficient of variation of about 10% due to the increased variability of a dried filter paper sample compared with other biochemical samples. The haematocrit is an additional variable not able to be measured. Also of importance is obtaining a balance between the sensitivity and specificity of each assay. Fixing cut-off points for action needs consideration of what is an acceptable percentage of the population to recall for further testing. Few assays are 100% discriminatory. Programs in Australasia currently screen for at least 30 disorders. Detection of these requires not only the assay of a primary marker but often determination of a ratio of that marker with another, or possibly an alternative assay, for example a DNA mutation. The most important disorders screened for are described briefly: phenylketonuria, primary congenital hypothyroidism, cystic fibrosis, the galactosaemias, medium-chain acyl-CoA dehydrogenase deficiency, glutaryl-CoA dehydrogenase deficiency and congenital adrenal hyperplasia, together with several other disorders detectable by tandem mass spectrometry. Newborn screening deals with rare disorders and benefit cannot be shown easily without very large pilot studies. There have been randomised controlled trials of screening for cystic fibrosis, and now several studies are beginning to establish the benefit of tandem mass spectrometry screening for disorders of fatty acid and amino acid metabolism. Two things will influence the new directions for newborn screening: the development of effective treatments for hitherto untreatable disorders, and advancing technology, enabling new testing strategies to be developed. There are novel treatments on the horizon for many discrete disorders. Susceptibility testing has recently been considered for newborn screening application, but is more controversial. Newborn screening has entered a new and exciting phase, with an explosion of new treatments, new technologies, and, possibly in the future, new preventive strategies.
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PMID:Newborn screening. 1820 33


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