Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Tandem mass spectrometry is an analytical method which is being implemented for neonatal screening. The method can determine the content of amino acids and acylcarnitines in neonatal screening samples in one integrated analysis. This allows detection of more than 20 inherited disorders of amino acid, fatty acid and organic acid metabolism. The aggregate incidence of these disorders is in the order of 1:4000. The principal disease which is detectable is medium-chain acyl-CoA dehydrogenase deficiency, which has an incidence of 1:10,000-1:20,000 in Northern Europe. Medium-chain acyl-CoA dehydrogenase deficiency puts the affected at risk of life-threatening metabolic crises, which are preventable if the condition has been diagnosed. Hence, the prognosis is excellent. The central theme for therapeutic management of medium-chain acyl-CoA dehydrogenase deficiency is carbohydrate supplementation, especially in situations of intercurrent illness. Tandem mass spectrometry screening will also enhance the present screening for phenylketonuria which employs a bacterial assay: the screening sample can be obtained 48-72 hours post partum, the false-positive rate will be reduced, and there will be no interference with antibiotics. Tandem mass spectrometry is being used in state-mandated screening panels in a few places and is being tested in pilot studies in many other places. A national prospective pilot project was launched on February 1, 2002 in Denmark. The project includes tandem mass spectrometry screening for galactosemia. In addition to neonatal screening, tandem mass spectrometry can be used for investigation of metabolic diseases, sudden unexpected death of infancy and shaken baby syndrome. Critical appraisal of tandem mass spectrometry will lead to improved health for infants affected by rare inherited disorders of metabolism.
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PMID:[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry]. 1252 3

Tandem mass spectrometry offers the chance to improve newborn screening (NBS) for phenylketonuria and to expand screening programmes at minimal additional costs. So far, however, there are only limited data available on the incidence of a broader range of disorders presently being considered, their natural course, the benefits achievable and potential harm associated with screening. Based on a literature search and experience from the Bavarian extended screening trial, these questions are addressed using medium-chain acyl-CoA dehydrogenase deficiency (MCADD) as an example. The data retrieved are sufficient for estimation of the incidence of MCADD cases identifiable by NBS and for diagnosis following clinical symptoms. Clinically detected cases ascertained by active surveillance in populations with highly developed and freely accessible health care systems consistently amount to only 33% of those identified by NBS. This difference cannot be explained by the difference in the proportion of the homozygous 985A-->G mutation, which accounts for about 50% of cases identified in NBS. Further research is needed to assess the contribution of MCADD to unexplained deaths in infancy. Retrospective cohort studies enrolling at least 500,000 children would allow for a more precise estimate of the natural course of disease in particular with regard to less severe adverse outcomes. The most relevant gap in knowledge concerns the long-term outcome of children identified following symptoms and by newborn screening. Since randomised controlled trials are unlikely to be feasible on this issue, a standardised documentation protocol should be implemented in follow-up studies for cases identified either by high risk screening or newborn screening. A proposal for the content of such observational studies is made.
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PMID:Data required for the evaluation of newborn screening programmes. 1461 87

In a trial running since October 2003 in the Dutch provinces of Friesland, Groningen, Drenthe and Overijssel neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has been added to the regular newborn screening programme for phenylketonuria, congenital hypothyroidism and adrenogenital syndrome. One of the questions to be answered by this trial is the cause of the strong variation in clinical expression of the disorder. Underdiagnosing is an important factor in this phenomenon, as shown by the data of a family of which the case histories of the two oldest children were discussed in this journal in 1965. Both children died at a very young age. Recently, MCAD deficiency was diagnosed in the youngest child of this family, now a 34-year-old woman. This family history illustrates the variable clinical expression of MCAD deficiency, which can cause death but can also run a milder or even subclinical course. Moreover, this family history shows that the underdiagnosis of MCAD deficiency in deceased children may be a cause of the apparently limited clinical detection rate of this disease, for which a simple treatment consisting of life-style and dietary measures is available after diagnosis.
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PMID:[Deficiency of the fatty-acid oxidising enzyme medium-chain acyl-CoA dehydrogenase (MCAD) in an adult, detected during a neonatal screening programme]. 1555 14

The incorporation of tandem mass spectrometry (MSMS) into an existing newborn screening program is an evolving process. Limited worldwide experience has ensured that all stages of reliability testing need to be followed. These include a literature review to establish methodology and analytes/disorders for testing and a pilot screening project including assaying archival samples from subjects with proven target disorders. Algorithms used for analyte concentrations and the relationships of various analytes to one another for resample criteria need to be continually reassessed to maximise screening specificity, sensitivity and positive predictive value. Since 1st of April 1998, the NSW Newborn Screening Program has screened 320, 848 babies using electrospray MSMS for selected amino acids and acyl camitines. Screening for amino acids has led to requests for 415 repeat samples with 94 babies referred for further testing. Of these 73 had a disorder of amino acid metabolism, including 43 with persistent hyperphenylalaninemia (36 of whom had PKU, 2 had a pterin pathway defect, 5 HPAA). Screening for acyl carnitines has led to requests for 245 repeat samples with 63 babies referred for further investigation. Of these 44 had a diagnosed disorder, including 15 with medium chain acyl CoA dehydrogenase deficiency. Five babies with confirmed disorders detectable with MS/MS had negative test results. The cost of screening using MSMS was only $A0.50 more than the method for screening for PKU and homocystinuria alone (ie the bacterial inhibition assays) and has allowed detection of an additional 74 babies at least 48 of whom have a diagnosis for which early treatment seems clearly beneficial. MSMS has shown a sensitivity of 95.9% and specificity of 99.8% in our laboratory with a positive predictive value of 18%.
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PMID:Newborn screening--is it really that simple? 1590 11

In newborn errors of metabolism, biomarkers are urgently needed for disease screening, diagnosis, and monitoring of therapeutic interventions. This article describes a 2-step approach to discover metabolic markers, which involves (1) the identification of marker candidates and (2) the prioritization of them based on expert knowledge of disease metabolism. For step 1, the authors developed a new algorithm, the biomarker identifier (BMI), to identify markers from quantified diseased versus normal tandem mass spectrometry data sets. BMI produces a ranked list of marker candidates and discards irrelevant metabolites based on a quality measure, taking into account the discriminatory performance, discriminatory space, and variance of metabolites' concentrations at the state of disease. To determine the ability of identified markers to classify subjects, the authors compared the discriminatory performance of several machine-learning paradigms and described a retrieval technique that searches and classifies abnormal metabolic profiles from a screening database. Seven inborn errors of metabolism-- phenylketonuria (PKU), glutaric acidemia type I (GA-I), 3-methylcrotonylglycinemia deficiency (3-MCCD), methylmalonic acidemia (MMA), propionic acidemia (PA), medium-chain acylCoAdehydrogenase deficiency (MCADD), and 3-OH long-chain acyl CoA dehydrogenase deficiency (LCHADD)-were investigated. All primarily prioritized marker candidates could be confirmed by literature. Some novel secondary candidates were identified (i.e., C16:1 and C4DC for PKU, C4DC for GA-I, and C18:1 forMCADD), which require further validation to confirm their biochemical role during health and disease.
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PMID:Biomarker discovery, disease classification, and similarity query processing on high-throughput MS/MS data of inborn errors of metabolism. 1631 8

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

The development of electrospray tandem mass spectrometry (MS-MS) has greatly increased the number of diseases that can be detected by newborn blood-spot screening. Different countries are introducing the technology at different rates and for different disease panels. Current policies in the United Kingdom, Germany and the United States are taken as examples. In the United Kingdom, many laboratories are using MS-MS for routine screening for phenylketonuria but, except for those participating in a two-year pilot study of screening for medium-chain acyl-CoA dehydrogenase deficiency, are forbidden use MS-MS to screen for other disorders. In Germany there has been considerable experience of MS-MS screening for a wide range of diseases, but recently the Federal Ministry for Health and Social Security prescribed a much more restricted disease panel, with the instruction that any other diagnostic results are to be suppressed and not reported. By contrast, a recent report from the American College of Medical Genetics, still being debated, recommends screening procedures that will detect an extremely broad range of disorders, including some that are very rare or of unproven clinical significance. The lack of even broad concordance at the level of national policy is extremely disturbing. Though all discussion is nominally founded on the ten principles laid down by Wilson and Jungner in 1968, there seems no generally accepted way of using these principles, or derived criteria, as objective decision tools. Alternative, less categorical, approaches are needed: the disorders concerned are not homogeneous entities and there may be advantages to screening other than reducing morbidity or mortality.
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PMID:International perspectives on newborn screening. 1676 7

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


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