FIG4-Associated Yunis-Varon Syndrome: Identification of a Novel Missense Variant.

Yunis-Varon syndrome (YVS; OMIM 216340) is a rare heterogeneous autosomal recessive disorder with easy recognition of characteristic severe neurological and skeletal abnormalities involving skeletal muscles and cartilages. This cleidocranial dysplasia is characterized by bone and tooth disorders; it also affects the cardiovascular system and tissues from ectoderm with very poor outcomes. Rarely, mutations of the FIG4 gene, encoding a 50-phosphoinositide phosphatase have been identified as the cause for YVS. We report a neonate born to a consanguineous couple with typical clinical manifestations of YVS. Using whole-exome sequencing, we identified a novel homozygous missense variant (c.968A>G; p.Gln323Arg) in the FIG4 gene. Thus, our study expands the molecular and genetic spectrum of FIG4-associated mutations. To our knowledge, this is the first reported case of YVS from the Saudi population.

Total parenteral nutrition-associated cholestasis and risk factors in preterm infants.

BACKGROUND/AIM: Development of hepatic dysfunction is a well-recognized complication of total parenteral nutrition in preterm infants. Previous studies reported the incidence of total parenteral nutrition-associated cholestasis and described possible contributing factors to its pathogenesis, but little is done trying to determine its possible predictive risk factors. The aims of this study was to determine the incidence of total parenteral nutrition-associated cholestasis and to develop a possible predictive model for its occurrence. PATIENTS AND METHODS: A review of medical records of all very low birth weight infants admitted to neonatal intensive care unit at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2001 and December 2003 was carried out. The infants were divided into two groups: Cholestasis and noncholestasis, based on direct serum bilirubin level >34 µmol/L. A multivariate logistic regression analysis was performed to calculate the statistical significance of risk factors. Receiver-operating characteristic curve was used to determine the optimal cutoff points for the significant risk factors and to calculate their sensitivity and specificity. The level of significance was set at P ≤ 0.05. RESULTS: A total of 307 patients were included in the analysis. The incidence of cholestasis in the whole population was 24.1% (74 patients). Infants with cholestasis had a lower birth weight, 735.4 ± 166.4 g vs. 1185.0 ± 205.6 g for noncholestasis group (P < 0.001), whereas the mean gestational age for the two groups was 25.4 ± 2.1 week and 28.9 ± 2.1 week, respectively (P < 0.001). The significant risk factors for the development of cholestasis were birth weight (P = 0.006) with an odds ratio of 0.99 [95% confidence interval (CI), 0.98, 0.99]; sensitivity of 92%, specificity of 87%; and total parenteral nutrition duration (P < 0.001) with an odds ratio of 1.18 (95% CI, 1.10, 1.27); sensitivity of 96%, specificity of 89%. CONCLUSIONS: A lower birth weight and longer duration of total parenteral nutrition were strong predictive risk factors for the development of cholestasis in preterm infants.

Induced hypothermia to treat neonatal hypoxic-ischemic encephalopathy. Review of literature with meta-analysis and development of national protocol.

The efficacy of induced hypothermia to treat hypoxic-ischemic encephalopathy (HIE) in term infants has been evaluated in 6 multicenter randomized controlled trials. Meta-analysis of these trials shows that hypothermia in the first 6 hours after moderately severe HIE reduced the risk rate of death or neurological impairment at 18 months of age; risk ratio (RR): 0.81 (95% confidence interval [CI]: 0.71 to 0.93, p=0.002); risk difference -0.11 (95% CI: -0.18 to -0.04), with a number needed to treat of 9 (95% CI: 5-25). It also showed that treatment with hypothermia was associated with an increased rate of intact survival; RR: 1.53 (95% CI: 1.22-1.93, p<0.001); risk difference: 0.12 (95% CI: 0.06-0.18), with a number need to treat of 8 (95% CI: 5-17). We developed a national protocol using a simplified method of cooling. This protocol will hopefully lead to a widespread implementation of induced hypothermia in different settings within Saudi Arabia.

High-frequency ventilation in the management of very-low-birth-weight infants with pulmonary hemorrhage.

Severe hypoxic respiratory failure secondary to massive pulmonary hemorrhage (MPH) in preterm infants could be fatal. The aim of this study was to assess the efficacy of high-frequency ventilation (HFV) as a rescue therapy for respiratory failure secondary to MPH in very-low-birth-weight (VLBW) infants. Prospectively we followed up all VLBW infants with pulmonary hemorrhage between January 1993 and December 1996 in our neonatal intensive care unit at King Khalid University Hospital. Seventeen VLBW infants with severe hypoxic respiratory failure secondary to MPH were treated with HFV. Ten (59%) infants responded to HFV and survived, while the other 7 (41%) did not respond and expired. Patent ductus arteriosus was considered the most common associated condition in 10 infants (59%). There were no statistically significant differences between the responders and the nonresponders in regard to gestational age, birth weight, sex ratio, % inborn, and primary diagnosis. However, preintervention peak inspiratory pressure (pip), arterial-alveolar ratio (a/A ratio) and oxygenation index (OI) were higher in the nonresponders ( p = 0.02, p = 0.03, and p = 0.003, respectively), while pip, F IO(2), pa CO(2), a/A ratio and OI were significantly lower than the nonresponders 3 hours postintervention ( p = 0.008, p = 0.006, p = 0.0002, p = 0.0005, and p = 0.0007, respectively). In conclusion, HFV might be an effective and lifesaving mode of treatment in VLBW infants with respiratory failure secondary to MPH; therefore, prospective randomized controlled trials are needed to confirm these findings.