Forms for 703 enrolled infants from 11 centers were received by the steering committee. All 94 patients from one of the centers were excluded because of violation of the inclusion criteria in 86 of these. Therefore, the final number of infants enrolled in the study was 609 (from 10 centers), with 288 in the room air group and 321 in the oxygen group. Median (5 to 95 percentile) gestational ages were 38 (32.0 to 42.0) and 38 (31.1 to 41.5) weeks (NS), and birth weights were 2600 (1320 to 4078) g and 2560 (1303 to 3900) g (NS) in the room air and oxygen groups, respectively. There were 46% girls in the room air and 41% in the oxygen group (NS). Mortality in the first 7 days of life was 12.2% and 15.0% in the room air and oxygen groups, respectively; adjusted odds ratio (OR) = 0.82 with 95% confidence intervals (CI) = 0.50-1.35. Neonatal mortality was 13.9% and 19.0%; adjusted OR = 0. 72 with 95% CI = 0.45-1.15. Death within 7 days of life and/or moderate or severe hypoxic-ischemic encephalopathy (primary outcome measure) was seen in 21.2% in the room air group and in 23.7% in the oxygen group; OR = 0.94 with 95% CI = 0.63-1.40. (ABSTRACT TRUNCATED)

To test the hypothesis that room air is superior to 100% oxygen when asphyxiated newborns are resuscitated, 84 neonates (birth weight > 999 g) with heart rate < 80 and/or apnea at birth were allocated to be resuscitated with either room air (n = 42) or 100% oxygen (n = 42). Serial, unblinded observations of heart rates at 1, 3, 5, and 10 min and Apgar scores at 1 min revealed no significant differences between the two groups. At 5 min, median (25th and 75th percentile) Apgar scores were higher in the room air than in the oxygen group [8 (7-9) versus 7 (6-8), p = 0.03]. After the initial resuscitation, arterial partial pressure of oxygen, pH, and base excess were comparable in the two groups. Assisted ventilation was necessary for 2.4 (1.5-3.4) min in the room air group and 3.0 (2.0-4.0) min in the oxygen group (p = 0.14). The median time to first breath was 1.5 (1.0-2.0) min in both the room air and oxygen groups (p = 0.59), and the time to first cry was 3.0 (2.0-4.0) min and 3.5 (2.5-5.5) min in the room air and oxygen groups, respectively (p = 0.19). Three neonates in the room air group and four in the oxygen group died in the neonatal period. At 28 d, 72 of the 77 surviving neonates were available for follow-up (36 in each group), and none had any neurologic sequelae.(ABSTRACT TRUNCATED AT 250 WORDS)

L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n 5 106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondiseaserelated variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/ patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.

There were no significant differences in somatic growth or neurologic handicap at an age of 18 to 24 months in infants resuscitated with either 21% or 100% O2 at birth. Based on these data, resuscitation with ambient air seems to be safe, at least in most cases. More studies are needed to settle this issue.

Complex III (cytochrome bc1) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T>A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T>A mutation has a causal role in complex III deficiency.