Disease relevance of Neonatal Screening

• METHODS: We reviewed the results of neonatal screening for homocystinuria over a period of 32 years in New England. Additional specimens were requested for repeated analysis when blood methionine measurements were at or above the established cutoff level [1].
• The effects of neonatal diagnostic screening on cystic-fibrosis (CF) -related morbidity were evaluated by comparing hospital admissions for CF-related illness in the first 2 years of life in 40 patients detected by means of neonatal screening and 56 patients born in the 3 years before screening began [2].
• Thus, autosomal recessive SR deficiency leads to BH(4) and to neurotransmitter deficiencies without hyperphenylalaninemia and may not be detected by neonatal screening for phenylketonuria [3].
• Fluorometric quantitative tyrosine determination on dried-blood spots is the primary neonatal screening test used for tyrosinemia type I (HT) in the province of Quebec [4].
• We have previously reported that despite neonatal screening, children with severe congenital hypothyroidism treated at 5 weeks of age with 6 micrograms/kg.day levothyroxine have clinically significant intellectual impairment, whereas those with the moderate form of the disease are indistinguishable from controls [5].

Psychiatry related information on Neonatal Screening

• The identification of alpha 1 antitrypsin deficiency (ATD) by neonatal screening was hypothesized to have had negative long-term effects on the mother-child relationship [6].
• As the possibility for expanding CF neonatal screening to other states is considered, the need for further exploration of psychosocial sequelae affecting parenting will be increasingly important [7].
• Psychological factors in cost-benefit analysis of somatic prevention. A study of the psychological effects of neonatal screening for alpha 1-antitrypsin deficiency [8].

High impact information on Neonatal Screening

• CONCLUSIONS: A cutoff level for blood methionine of 1 mg per deciliter in neonatal screening tests for homocystinuria should identify affected infants who have only slightly elevated concentrations of methionine and reduce the frequency of false negative results [1].
• Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program [9].
• CONCLUSIONS: In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the organism was isolated from respiratory secretions [10].
• We detected GRTH at birth by analysis of blood obtained during routine neonatal screening [11].
• Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine catabolism that appears to be the most frequent organic aciduria detected in tandem mass spectrometry-based neonatal screening programs [12].

Chemical compound and disease context of Neonatal Screening

• Concentrations of phytanic acid and pristanic acid were measured in stored dried blood spots collected at neonatal screening from patients with peroxisomal disorders, and compared with concentrations in control blood spots [13].
• BACKGROUND: Hereditary tyrosinemia type I (HT) fulfills the criteria for inclusion in neonatal screening programs, but measurement of tyrosine lacks clinical specificity and quantitative assay of succinylacetone is laborious [14].
• Measurement of phytanic acid and pristanic acid and their ratios in stored dried blood collected at neonatal screening can therefore be used in the diagnosis of peroxisomal disorders, especially for those cases in which, owing to early death of the patient, no other material is available for biochemical investigations [13].
• Effect of single and multiple courses of prenatal corticosteroids on 17-hydroxyprogesterone levels: implication for neonatal screening of congenital adrenal hyperplasia [15].
• Measurement of free carnitine and acylcarnitines allows the detection of several inborn errors of metabolism in neonatal screening [16].

Biological context of Neonatal Screening

• We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal screening samples [17].
• In order to investigate whether individuals with this disorder have small deletions, additions, or point mutations in the histidase gene, we screened genomic DNA isolated from 50 histidinemic individuals who were discovered by the neonatal screening program [18].
• Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency [19].
• Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving [20].
• From a practical viewpoint, the genetic analysis of blood-spots collected on Guthrie cards for neonatal screening for PKU could be a simple method to establish the genotype of neonates [21].

Anatomical context of Neonatal Screening

• Fifty-four subjects with congenital hypothyroidism detected during neonatal screening and associated with an ultrasound or scintiscan picture of thyroid dysgenesis were investigated for PAX8 mutations [22].
• Modification of neonatal screening test for erythrocyte glucose-6-phosphate dehydrogenase deficiency [23].
• A neonatal screening program for CF by determination of albumin in meconium was performed in the north eastern part of the Netherlands from 1973 to 1979 [24].

Associations of Neonatal Screening with chemical compounds

• 4 had been diagnosed by routine neonatal screening and started a low phenylalanine diet in infancy [25].
• We conclude that genotyping is a valuable diagnostic tool and a good complement to neonatal screening, especially in confirming or discarding the diagnosis in cases with slightly elevated 17-hydroxyprogesterone levels [26].
• Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population [27].
• Retrospective analysis of the neonatal screening samples of 2 additional known patients revealed increased succinylacetone concentrations of 46 and 169 micromol/L, respectively [28].
• All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values [29].

Gene context of Neonatal Screening

• Applications of dystrophin testing include improved diagnostic accuracy, carrier detection, fetal diagnosis, and evaluation of asymptomatic male infants identified as a result of neonatal screening for increased serum creatine kinase levels [30].
• This disease warrants early detection through neonatal screening program, since the beneficial effect of early administration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR deficiency [31].
• Fumarylacetoacetase (FAH) (E.C.3.7.1.2) was measured retrospectively by an ELISA on 25 dried-blood samples from proven patients with HT and prospectively in 72,000 specimens received in the neonatal screening program [4].
• We report here two new mutations in exon 11 of the PAH gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia [32].
• We have retrospectively analyzed 837 random anonymized dried blood spot (DBS) samples from neonatal screening programs in Scandinavia for mutations in HFE, the candidate gene for hemochromatosis [33].

Analytical, diagnostic and therapeutic context of Neonatal Screening

• To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program [34].
• METHODS: A total of 36 patients from 10-15.5 years old who were enrolled in the screened or control group of the Wisconsin CF Neonatal Screening Project completed the CHQ [35].
• Retrospective study of the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Guthrie cards from a large cohort of neonatal screening for cystic fibrosis [36].
• This work constitutes the first study able to provide a precise measure of CF birth prevalence and of its evolution through the combined effects of neonatal screening, prenatal diagnosis, ultrasound examination and family testing [37].
• To understand better the events associated with the initiation of lung disease in young children with cystic fibrosis (CF), we prospectively performed a longitudinal study examining the early bacteriologic, immunologic, and clinical courses of 42 children with CF diagnosed after identification by neonatal screening [38].

References