Application of a second-tier newborn screening assay for c5 isoforms.

We report a case of false-positive metabolic screening for isovaleric acidemia in a newborn due to treatment of the mother with pivalic acid containing antibiotics before delivery. By using a recently established second-tier test based on the tandem-MS technique, we could identify pivalic acid in a dried blood sample taken during routine neonatal screening. Before this second-tier test was initiated, diverse analytical procedures were performed in the baby to rule out isovaleric acidemia and carnitine supplementation was started. This caused additional psychological burden to the family. The direct use of the second-tier test would have avoided these negative consequences of a false-positive screening result.

Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Neonatal screening programs for congenital adrenal hyperplasia (21-CAH) using an immunoassay for 17alpha-hydroxyprogesterone (17-OHP) generate a high rate of positive results attributable to physiological reasons and to cross-reactions with steroids other than 17alpha-OHP, especially in preterm neonates and in critically ill newborns. METHODS: To increase the specificity of the screening process, we applied a liquid chromatography-tandem mass spectrometry method quantifying 17alpha-OHP, 11-deoxycortisol, 21-deoxycortisol, cortisol, and androstenedione. The steroids were eluted in aqueous solution containing d8-17alpha-OHP and d2-cortisol and quantified in multiple reaction mode. RESULTS: Detection limit was below 1 nmol/liter, and recovery ranged from 64% (androstenedione) to 83% (cortisol). Linearity was proven within a range of 5-100 nmol/liter (cortisol, 12.5-200 nmol/liter), and total run time was 6 min. Retrospective analysis of 6151 blood samples and 50 blood samples from newborns with clinically confirmed 21-CAH, as well as prospective analysis of 1609 samples of a total of 242,500 testing positive in our routine 17-OHP immunoassay, allowed clear distinction of affected and nonaffected newborns. High levels of 21-deoxycortisol were only found in children with 21-hydroxylase deficiency. Calculating the ratio of 17alpha-OHP to 21-deoxycortisol divided by cortisol further increased the sensitivity of the method. CONCLUSION: Our liquid chromatography-tandem mass spectrometry procedure as a second-tier test can be used to reduce false-positive results of standard 21-CAH screening. The short total run time of 6 min allows for immediate reanalysis of all immunoassay results above the cutoff.

Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands.

Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene (AGL). For most populations, none of the AGL mutations described to date is particularly frequent. In this paper, we report that six children with GSD IIIA from the Faroe Islands were found to be homozygous for the novel nonsense mutation c.1222C>T (R408X) of the AGL gene. This mutation is easily detected by restriction enzyme digest with NsiI after mismatch PCR. Investigating five intragenic polymorphisms, we could show that this mutation was always associated with the same haplotype. The c.1222C>T mutation could be detected on two chromosomes of another 50 unselected GSD IIIA patients of other European or North American origin which means that this mutation plays a minor role worldwide. From the fact that we are currently aware of a total of 14 GSD IIIA cases in the Faroese population of 45 000, the observed prevalence is 1 : 3100. While the novel AGL mutation c.1222C>T was not detectable among 198 German newborns, nine out of 272 children from the Faroese neonatal screening program were found to be heterozygous for this mutation. Thus, the calculated prevalence is 1 : 3600 (95% CI 1:700-1:6400). We conclude that due to a founder effect, the Faroe Islands have the highest prevalence of GSD IIIA world-wide. The detection of the molecular defect has facilitated the diagnosis and has offered the opportunity for prenatal diagnosis in this patient group.

Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants.

BACKGROUND: Marine food provides essential fatty acids that are important during pregnancy, but the benefits may be limited at high intakes and by seafood contaminants. METHODS: In the fishing community of the Faroe Islands, 182 pregnant women with spontaneous singleton births were consecutively recruited for a cohort in 1994- 1995. Concentrations of fatty acids and seafood contaminants in blood samples were analysed as predictors of gestational length and birthweight. RESULTS: Serum concentrations of eicosapentaenoic acid (EPA) increased with maternal marine food intake, while the tendency was less clear for docosahexaenoic acid (DHA). An increase in the relative concentration of DHA in cord serum phospholipids by 1% was associated with an increased duration of gestation by 1.5 days (95% CI : 0.7-2.2). However, birthweight adjusted for gestational length decreased by 246 g (95% CI : 16-476) for each increase by 1% of the EPA concentration in cord serum. Concentrations of the seafood pollutants mercury and polychlorinated biphenyls (PCB) were associated with fatty acids levels, but the contaminants did not appear to affect any of the outcome parameters. CONCLUSION: An increased intake of marine fats appears to prolong the duration of gestation, but birthweight adjusted for gestational age may decrease at high intake levels. This effect does not seem to be due to increased exposures to seafood contaminants.

Maternal seafood diet, methylmercury exposure, and neonatal neurologic function.

OBJECTIVE: To determine whether neonatal neurologic function is adversely affected by seafood contaminants from maternal diet during pregnancy. STUDY DESIGN: One hundred eighty-two singleton term births were evaluated in the Faeroe Islands, where marine food includes pilot whale. Maternal serum, hair, and milk and umbilical cord blood were analyzed for contaminants. Levels of essential fatty acids, selenium, and thyroid hormones were determined in cord blood. Each infant's neurologic optimality score was determined at 2 weeks of age adjusted for gestational age, and predictors were assessed by regression analysis. RESULTS: Exposures to methylmercury and polychlorinated biphenyls were increased in relation to maternal seafood intake, as were omega3 fatty acid concentrations in cord serum. Thyroid function was normal. After adjustment for confounders, a 10-fold increase of the cord-blood mercury concentration was associated with a decreased neurologic optimality score of 2.0 (P =. 03). This effect corresponds to a decrease in gestational age of about 3 weeks. Other indicators of the seafood diet had no effect on this outcome. CONCLUSIONS: Prenatal exposure to methylmercury from contaminated seafood was associated with an increased risk of neurodevelopmental deficit. Thus in this North Atlantic population, methylmercury constituted an important neurologic risk factor, although effects of other seafood components were not detectable.

[The body image of children of nursery school age]. / Körpervorstellungen von Kindergartenkindern.

Both from the view of the pediatrician (16) and the child analyst (3, 6, 9, 21), and recently, too, by behavioral biologists (15) the emotional aspects of illness and hospitalization have been treated with increasing differentiation. On the other hand there are only few studies regarding the cognitive aspects of the problem, i.e. the concepts children have of their bodies and of illness, which depend on the momentary level of their intellectual development. Children's ideas and fears arising from illness or hospitalization frequently can only be understood with the knowledge of the actual body-image. Therefore we have tried to investigate by interviews and drawings of three- to seven-year-old preschoolers their conceptions of the interior of the body and its function. The sources of these ideas were discussed and some suggestions were made how the results of the study could be used in hospital and kindergarten.