Newborn screening

Chance DH, Adam BW, Smith SJ, Alexander JR, Hillman SL, Hannon WH (1999) Validation of accuracy-based amino acid reference materials in dried-blood spots by tandem mass spectrometry for newborn screening assays. Clin Chem 45 1269-1277. 

In many localities, newborn screening has become standard for this disorder, which in the general population has an approximate incidence of 1/250,000 live births. Carrier detection is possible, either by measurement of enzymatic activity in cultured fibroblasts or by study of restriction endonuclease fragments of DNA. Antenatal testing is also available. 

This in fact is what happened. Tandem MS has clearly been shown to be the only technology to screen for disorders of fatty acid oxidation and could also detect many disorders of organic acid metabolism. Tandem MS has the ability to detect both compound classes (amino acids and acylcarnitines) and after demonstrating that both classes could be prepared in the same manner, the MS/MS analysis of blood spots for newborn screening applications was born. 

In addition to explaining verbally the concepts of mass spectrometry, it is also helpful to explain them visually. Two ideas utilized in newborn screening, for example, is the ability of a mass spectrometer to sort molecules by their mass and determine how many of these compounds are present. One illustration uses coins while another uses jelly beans. Instructions on how to prepare and present these experiments are shown below. 

Northwest Regional Newborn Screening Program http //oregon.gov/DHS/ph/nbs/docs/isobutyrylcoa.pdf... 

ACTion Sheets - Newborn screening follow up (1 link) http //ghr.nlm.nih.gov/condition=isobutyrylcoenzymeadehydrogenasedeficiency/sho w/ACTion+Sheets jsessionid=lE72C905CF226DFC5B56841BC3C34748... 

Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bah D, McDonald MT, Kishnani PS, Chen YT, Millington DS. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003 Aug 54(2) 219-23. Epub 2003 May 7. PubMed citation... 

Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders. 

Newborn screening tests are done on a small blood sample, which is taken by pricking the baby s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. 

Mandatory newborn screening for PKU has allowed early detection and mitigation of the most severe effects In most cases. 

Encyclopedia Newborn Screening Tests http www.nlm.nih.gov/medlineplus/ency/article/007257.htm... 

ACTion Sheets - Newborn screening foUow up (1 hnk) http /yghr.nlm.nih.gov/condition=mediumchainacylcoeiizymeadehydrogeiiasedeficie ncy/show/ACT ion+Sheets j sessionid=6BDA7E381EFlDD0A071F5FFBE9B0A809... 

Dezateux C. Newborn screening for medium chain acyl-CoA dehydrogenase deficiency evaluating the effects on outcome. Eur J Pediatr. 2003 Dec 162 Suppl l S25-8. Epub 2003 Nov 20. Review. PubMed citation... 

Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase deficiency in 275 000 babies. 

Genotypic differences of MCAD deficiency in the Asian population novel genotype and clinical symptoms preceding newborn screening notification. 

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF (2003) Expanded newborn screening for inborn errors of metabolism by electrospray ionization - tandem mass spectrometry results, outcome, and implications. Pediatrics 111 1399-1406... 

Recommended specimen information, in addition to mandatory patient identifiers, include age, date and time of collection, reason for the request (i.e., confirmatory testing following an abnormal newborn screening result), and clinical status. Knowledge of clinical status at the time of specimen collection is essential when a STAT analysis is requested (i.e., when results are required within 2-3 h), because specimens for metabolic investigations may not have been secured ahead of aggressive therapeutic intervention. Specimens collected even after a partial recovery may not reveal diagnostic abnormalities that are more readily detectable, under acute conditions. 

Acylcarnitine analysis for the diagnosis of organic acidemias and particularly of FAO disorders plays an increasingly prominent role in all venues of clinical biochemical genetics prenatal diagnosis, newborn screening, evaluation of symptomatic patients, and postmortem screening. Almost exclusively performed by tandem... 

Ensenauer R, Vockley J, Willard JM, et al (2004) A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet 75 1136-1142... 

Oglesbee D, He M, Majumder N, et al (2007) Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet Med 9 108-116... 

Matern D, Strauss AW, Hillman SL, Mayatepek E, Millington DS, Trefz FK (1999) Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. Pediatr Res 46 45-49... 

Browning MF, Larson C, Strauss A, Marsden DL (2005) Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects. J Inherit Metab Dis 28 545-550... 

Koeberl DD, Young SP, Gregersen NS, et al (2003) Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res 54 219-223... 

Matern D, He M, Berry SA, et al (2003) Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. Pediatrics 112 74-78... 

Abdenur JE, Chamoles NA, Guinle AE, Schenone AB, Fuertes AN (1998) Diagnosis of isovaleric acidaemia by tandem mass spectrometry false positive result due to pivaloylcarnitine in a newborn screening programme. J Inherit Metab Dis 21 624-630... 

Malvagia S, la Marca G, Casetta B, et al (2006) Falsely elevated C4-carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening. J Mass Spectrom 41 263-265... 

Severe plasma turbidity due to hyperlipidaemia, as found in lipoprotein lipase deficiency, was shown to result in false-positive newborn screening results when dried blood spots on filter paper are used, but does not usually affect the quantitative colorimetric assay employing plasma samples (reference [21] and our own unpublished experience). 

Moslinger D, Stockler-Ipsiroglu S, Scheibenreiter S, Tiefenthaler M, Miihl A, Seidl R, Strobl W, Plecko B, Suormala T, Baumgather ER (2001) Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Eur J Pediatr 160 277-282... 

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