A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy.

Pathogenic variants impacting upon assembly of mitochondrial respiratory chain Complex IV (Cytochrome c Oxidase or COX) predominantly result in early onset mitochondrial disorders often leading to CNS, skeletal and cardiac muscle manifestations. The aim of this study is to describe a molecular defect in the COX assembly factor gene COX18 as the likely cause of a neonatal form of mitochondrial encephalo-cardio-myopathy and axonal sensory neuropathy. The proband is a 19-months old female displaying hypertrophic cardiomyopathy at birth and myopathy with axonal sensory neuropathy and failure to thrive developing in the first months of life. Serum lactate was consistently increased. Whole exome sequencing allowed the prioritization of the unreported homozygous substitution NM_001297732.2:c.667 G > C p.(Asp223His) in COX18. Patient's muscle biopsy revealed severe and diffuse COX deficiency and striking mitochondrial abnormalities. Biochemical and enzymatic studies in patient's myoblasts and in HEK293 cells after COX18 silencing showed a severe impairment of both COX activity and assembly. The biochemical defect was partially rescued by delivery of wild-type COX18 cDNA into patient's myoblasts. Our study identifies a novel defect of COX assembly and expands the number of nuclear genes involved in a mitochondrial disorder due to isolated COX deficiency.

Severe sepsis in a premature neonate: protein C replacement therapy.

Treatment with activated protein C has been shown to reduce mortality in adult patients with severe sepsis but also to increase risk of bleeding. In patients with predisposition to bleeding, as in preterm infants, the inactivated form of protein C could serve as a safe therapeutic option. We report the case of a preterm neonate who developed severe sepsis on the 28th day of life, who was successfully treated with the inactivated form of protein C for a period of 96 hours.

Successful removal of catheter fragment from right atrium in a premature infant.

A premature infant with rupture of percutaneous central catheter and subsequent migration of the fragment in the right atrium was reported. Umbilical venous catheterization was safely used to remove the fragment.

Effects of volume-targeted synchronized intermittent mandatory ventilation on spontaneous episodes of hypoxemia in preterm infants.

BACKGROUND: Hypoxemic episodes in ventilated preterm infants are frequently caused by reduced ventilation due to a decrease in lung volume and acute worsening of respiratory mechanics. OBJECTIVE: To compare the efficacy of conventional time-cycled, pressure-limited flow synchronized intermittent mandatory ventilation (SIMV) and volume-targeted SIMV (VT-SIMV) in reducing the frequency and severity of these episodes. METHODS: SIMV and VT-SIMV were compared in preterm infants with frequent spontaneous episodes of hypoxemia. VT-SIMV was provided with the Draeger Babylog 8000plus ventilator in volume-guarantee mode. RESULTS: In all, 32 infants (birth weight 668 +/- 126 g, gestational age 24.8 +/- 1.1 weeks, age 37.5 +/- 17.3 days) were studied during 2-hour periods of SIMV and VT-SIMV in random sequence. In an initial phase, a group of 12 infants was supported during VT-SIMV with a target tidal volume of 4.5 ml/kg (VT-SIMV 4.5). A planned interim analysis did not show differences in frequency and duration of hypoxemia between VT-SIMV 4.5 and SIMV, and the initial phase was stopped. In a second phase of the study, 20 infants were studied while supported with a target tidal volume of 6.0 ml/kg during VT-SIMV (VT-SIMV 6.0). In the second phase of the study, the frequency of the hypoxemic episodes did not change but the mean episode duration was shorter during VT-SIMV compared to SIMV. The proportion of mechanical breaths with small tidal volumes (< or =3 ml/kg) was reduced during VT-SIMV 6.0 versus SIMV, while the peak inspiratory pressure and mean airway pressure were increased. CONCLUSION: VT-SIMV did not reduce the frequency of hypoxemic episodes, but VT-SIMV 6.0 was effective in reducing the duration of the hypoxemic episodes.

Risk factors for pulmonary candidiasis in preterm infants with a birth weight of less than 1250 g.

UNLABELLED: To evaluate the epidemiology of pulmonary candidiasis (PC) and to identify risk factors in premature infants during the 1st month of life, all infants with a birth weight <1250 g admitted to our neonatal intensive care unit with PC between January 1994 and December 2001 were retrospectively reviewed. Infants with PC ( n =20) were compared with a control group ( n =20), matched for gestational age and birth weight, with regard to possible perinatal and postnatal risk factors. Among 325 infants with a birth weight <1250 g, 20 out of 233 ventilated infants (8.6%) developed PC. Candida albicans ( n =12) and C. parapsilosis ( n =4) were the predominant isolates. Neonates with PC were significantly different from controls with regard to male prevalence ( P =0.002), rates of preterm premature rupture of membranes (PPROM) ( P =0.02), longer duration of antibiotic therapy ( P =0.01) and of ventilation ( P =0.02). The difference between groups did not attain significance with regard to postnatal dexamethasone administration, duration of central vein catheterisation and duration of parenteral nutrition. Multivariate logistic regression analysis indicated as significant predictors of PC, among perinatal data, the male gender (OR =26.3; 95%CI 2.44 to 284) and PPROM (OR =12.3; 95%CI 1.16 to 130) and, among postnatal data, the duration of ventilation (OR =1.54; 95%CI 1.01 to 2.34). CONCLUSION: The presence of preterm premature rupture of membranes and the duration of ventilation are significant risk factors for developing pulmonary candidiasis and should be considered in the preventive efforts to reduce this disease in infants with a birth weight <1250 g.