Neonatal screening

Table 65-1 shows the clinical features of SCT and SCD. SCD usually is identified by routine neonatal screening programs using hemoglobin electrophoresis, thin-layer isoelectric... 

She was diagnosed with sickle cell anemia at birth, identified through neonatal screening. Today, her hemoglobin is 8.6 g/dl (86 g/L or 5.3 mmol/L) and she is afebrile. 

SCD is usually identified by routine neonatal screening programs using isoelectric focusing. 

Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania neonatal screening shows high incidence and unexpected mutation frequencies. 

Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. 

Neonatal Screening The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by chnical or laboratory measures. A screening test is designed to sort out healthy neonates from those not weU, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic, [nih]... 

Millington DS, Kodo N, Norwood DL, Roe CR (1990) Tandem mass spectrometry a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis 13 321-324... 

Heard GS, Wolf B, Jefferson LG, Weissbecker KA, Nance WE, Secor McVoy JR, Napolitano A, Mitchell PL, Lambert FW, Linyear AS (1986) Neonatal screening for biotinidase deficiency results of a 1-year pilot study. J Pediatr 108 40-46... 

It has surprised this reviewer that in the effort to lower the rate of false-positive findings in neonatal screening and in young infants there has not been much attention paid to measurement of 21-deoxycortisol, another key analyte overproduced in CAH. 

Speiser PW (2004) Improving neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 89 3685-3686... 

Harms E, Olgemoller B (2011) Neonatal screening for metabolic and endocrine disorders. Dtsch Arztebl Int 108 11-22... 

During the past 20 years, neonatal screening programs using the Guthrie test for inborn errors of metabolism such as phenylketonuria have become more widely used. The characteristics of diseases in which mass screening is... 

Serum samples obtained from cord blood can be used, but small amounts of blood can be taken easily on filter paper by heel puncture and the dried blood sample on filter paper (blood disks) can be sent to special laboratories by mail. Therefore, the latter method is now widely used in neonatal screening programs. 

TBG in dried blood samples on filter paper is stable for at least 1 month when kept dry at room temperature. The mean coefficients of variation are 6.6% (within assay) and 5.9% (between assays). The concentrations of TBG in dried blood samples determined by this method correlated well with those in serum determined by radioimmunoassay (r = 0.95) and by enzyme immunoassay (r = 0.96). This method is applicable for detecting patients with congenital TBG deficiency who do not need to be treated and avoids the false-positive results obtained on neonatal screening with T4. 

Cystic fibrosis is a lethal autosomal recessive disorder in Caucasians, with an incidence of 1 2000 in the general population. Newborn babies with this disease have increased serum trypsin concentrations. Thus, Crossley et al. developed a radioimmunoassay for human trypsin in dried blood samples on filter paper and used it for neonatal screening for this disease (C9). A non-isotopic immunoassay, such as enzyme immunoassay of trypsin, will be developed for this purpose. 

C9. Crossley, J. R., Smith, P. A., Edgar, B. W., Gluckman, P. D., and Elliott, R. B., Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots. Clin. Chim. Acta 113, 111-121 (1981). 

Biotinidase deficiency met most of the criteria for inclusion in a neonatal screening program, such as ease and efficacy of treatment, frequency of the disorder, and the relatively low cost of testing. Therefore, a simple colorimetric method to determine biotinidase activity using the same soaked filter-paper blood... 

Wolf, B., Heard, G. S., Jefferson, L. G., Proud, V. K., Nance, W. E., and Weissbecker, K. A. (1985). Clinical findings in four children with biotinidase deficiency through a statewide neonatal screening programs. N. Engl. J. Med. 313,16-19. 

In the past few years, LC-MS has rapidly conquered the clinical laboratory, and further developments in this area are expected for the near future. Recent reviews [2-3] highhghted the importance of such developments. Application areas for LC-MS in the clinical laboratory are therapeutic drag monitoring, neonatal screening, reference methods, and toxicology. Today, one should add the rapidly developing area of clinical biomarker discovery to this list [4] (Ch. 18.6). 

In this chapter, we give a taste of the current state-of-the-art of LC-MS in clinical applications. Certainly not all possibilities and applications are discussed in this chapter. Topics discussed are therapeutic drag monitoring (Ch. 12.2) and neonatal screening (Ch. 13.2). In addition, the LC-MS analysis of various classes of drags of abuse, and systematic toxicological analysis are discussed. 

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