Mutations in the gene encoding the ATP binding cassette transporter member A3 (ABCA3) are associated with fatal surfactant deficiency. ABCA3 lines the limiting membrane of lamellar bodies within alveolar type-II cells, suggesting a role in surfactant metabolism. The objective of this study was to determine the surfactant phospholipid composition and function in patients with mutations in the ABCA3 gene. Bronchoalveolar lavage (BAL) fluid was analyzed from three groups of infants: 1) Infants with ABCA3 mutations, 2) infants with inherited surfactant protein-B deficiency (SP-B), and 3) patients without parenchymal lung disease (CON). Surfactant phospholipid profile was determined using twodimensional thin-layer chromatography, and surface tension was measured with a pulsating bubble surfactometer. Phosphatidylcholine comprised 41 Ϯ 19% of the total phospholipid in the BAL fluid of the ABCA3 group compared with 78 Ϯ 3% and 68 Ϯ 18%, p ϭ 0.008 and 0.05, of the CON and SP-B groups, respectively. Surface tension was 31.5 Ϯ 9.3 mN/m and was significantly greater than CON but no different from SP-B. We conclude that mutations in ABCA3 are associated with surfactant that is deficient in phosphatidylcholine and has decreased function, suggesting that ABCA3 plays an important role in pulmonary surfactant phospholipid homeostasis. (Pediatr Res 59: [801][802][803][804][805] 2006)

ABSTRACT:The prevalence of the common mutations in the surfactant protein-B (121ins2), surfactant protein-C (I73T), and ATP-binding cassette member A3 (E292V) genes in populationbased or case-control cohorts of newborn respiratory distress syndrome (RDS) is unknown. We determined the frequencies of these mutations in ethnically diverse population and disease-based cohorts using restriction enzyme analysis (121ins2 and E292V) and a 5Ј nuclease assay (I73T) in DNA samples from population-based cohorts in Missouri, Norway, South Korea, and South Africa, and from a case-control cohort of newborns with and without RDS (n ϭ 420). We resequenced the ATP-binding cassette member A3 gene (ABCA3) in E292V carriers and computationally inferred ABCA3 haplotypes. The population-based frequencies of 121ins2, E292V, and I73T were rare (Ͻ0.4%). E292V was present in 3.8% of newborns with RDS, a 10-fold greater prevalence than in the Missouri cohort (p Ͻ 0.001). We did not identify other loss of function mutations in ABCA3 among patients with E292V that would account for their RDS. E292V occurred on a unique haplotype that was derived from a recombination of two common ABCA3 haplotypes. E292V was over-represented in newborns with RDS suggesting that E292V or its unique haplotype impart increased genetic risk for RDS. (Pediatr Res 63: 645-649, 2008)

Aim:The objective of the present study was to develop a method for surface electromyographic (EMG) registration of muscle activity in infants, with the perspective of assessing neuromuscular function/prognosis in infants with obstetric brachial plexus palsy (OBPP).Method: Fifteen healthy infants, aged 1-4 days, were recruited for the study. EMG signals were registered from the biceps, triceps and palmar portion of thenar muscles on both arms and hands. For this purpose surface electrodes for bipolar recording were developed using two sintered Ag/AgCl pellets that had been cast in silicone rubber. The Moro reflex was used to elicit a standardised motor stimulus. The reflex was elicited 5 times, and during EMG recording the procedure was video taped. To define the onset of muscle activity the running block threshold method was adapted to time signals.Results: The custom-made electrodes performed well and EMG signals of good quality were obtained from the different sites. The onset algorithm worked automatically, giving stable and visually correct registration. The signals could clearly describe the onset of muscle activity during the Moro reflex with a symmetrical pattern in both arms and hands. The extension/abduction phase of the reflex was characterised by predominant activity in the triceps muscle with concomitant low-grade activity in the antagonistic biceps muscle. During the embracing phase, occurring up to 1 second after onset of abduction, the opposite pattern was seen. Thenar activation, causing flexion/opposition of the thumb, was salient only during the embracing phase.Conclusion: Surface EMG can be used in infants to objectively assess the normal motor pattern in muscles innervated by different branches of the brachial plexus. This convenient method shall be applied to evaluate the status and possibly the prognosis in infants with OBPP. (REF, nϭ56, GA 34Ϯ5 wks), and normal newborns (noRDS, nϭ167, GA 39Ϯ2 wks). We amplified a 637 base pair product that included codon 292 and subjected amplicons to BsrG1 restriction analysis and agarose gel electrophoresis. THE E292V VARIANT IN ABCA3 IS OVER-REPRESENTED IN NEWBORNS WITH RESPIRATORY DISTRESS SYNDROME (RDS)TResults: Excluding 1 each of concordant twins in the REF and noRDS groups, 3 RDS (2.4%), 5 REF (9.1%), and 2 noRDS (1.2%) infants were heterozygous for E292V (Pϭ0.009). Males and females were equally represented. One infant with E292V in the noRDS group was Black, all others with E292V were White. Symptomatic infants (REFϩRDS) with E292V were more mature than those without E292V (35Ϯ3 vs 32Ϯ5 wks, Pϭ0.007). Duration of mechanical ventilation, and need for supplemental oxygen were not significantly different. Infants with RDS and E292V developed pneumothoraces more frequently (78%) than infants with RDS but without E292V (9%) (PϽ0.001). Six infants had resolution of symptoms within 1 month of birth; the noRDS individuals with E292V remained asymptomatic.Conclusions: The E292V variant in ABCA3 is significantly more prevalent in infants with RDS than in ...