Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca2+ and Voltage-Activated K+ Channel Activity in Human Insulin Secretion.

Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca2+ and voltage-activated K+ channel (BKC). The KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K+ current. The phenotype of this variant includes developmental delay, and visceral and connective tissue malformations. So far, only three cases of LWAS have been described, one of which also had neonatal diabetes (ND). We present the case of a newborn affected by LIWAS carrying the p.(Gly375Arg) variant who manifested diabetes in the first week of life. The description of our case strongly increases the frequency of ND in LIWAS patients and suggests a role of BK inactivation in human insulin secretion. The knowledge on the role of BKC in insulin secretion is very poor. Analyzing the possible mechanisms that could explain the association of LIWAS with ND, we speculate that BK inactivation might impair insulin secretion through the alteration of ion-dependent membrane activities and mitochondrial functions in ß-cells, as well as the impaired intra-islet vessel reactivity.

Effects of Breathing and Apnoea during Sustained Inflations in Resuscitation of Preterm Infants.

BACKGROUND: A sustained inflation (SI) at birth in preterm babies may be ineffective unless the infants breathe. Gain in lung volume is associated with breathing during delivery room non-invasive management. OBJECTIVE: To describe the breathing patterns of preterm infants during an SI and correlate to a calculated gain in lung volume. METHODS: Retrospective observational study. Data collected from a respiratory function monitor during SI (25 cmH2O for 15 s then PEEP at 5 cmH2O) through a face mask in preterm infants (gestational age [GA] ≤31 weeks). Spontaneous breaths, inspiratory time (TI), inspiratory/expiratory tidal volume (Vti/Vte), and gain in lung volume were determined. RESULTS: 30 SIs in 20 infants (mean GA 27 weeks; birth weight 825 g) were analysed and stratified in 2 groups according to spontaneous breathing: SIs without spontaneous breaths (apnoea: n = 11) and SIs with spontaneous breaths (breathing: n = 19). Mean GA was lower in the apnoea group versus the breathing group (25 vs. 27+5 weeks; p = 0.01). Mean birth weight was lower in the apnoea group versus the breathing group (683 vs. 860 g; p = ns). In the breathing group, the mean number of spontaneous breaths was 4 with a mean TI of 0.52 min, the mean Vti/kg was 5.9 mL/kg, and the mean Vte was 2.7 mL/kg. The calculated mean gain in lung volume was 7.5 mL/kg in the apnoea group and 17.8 mL/kg in the breathing group (p = 0.039). CONCLUSIONS: Actively breathing infants during an SI at birth showed a gain in lung volume higher than apnoeic infants. Spontaneous breathing during SI seems to be related to GA.

Sustained Inflation and Its Role in the Delivery Room Management of Preterm Infants.

A noninvasive approach in the delivery room in place of intubation and mechanical ventilation can reduce rates of bronchopulmonary dysplasia and death. Nevertheless, the rate of nasal continuous positive airway pressure failure still remains high. In order to prevent lung injury and to enhance the success of continuous positive airway pressure, sustained inflation (administration by face mask or nasopharyngeal tube of a high peak pressure of 20-25 cm H2O, maintained for 10-15 s) has been recently proposed to establish an early and efficient functional residual capacity in the delivery room. Sustained inflation is an intriguing therapy, although the results of clinical trials are controversial in terms of respiratory outcomes. A critical role in the success of sustained inflation could be the presence of open or closed glottis and the contribution of spontaneous breathing that allows air to enter the lungs during the maneuver. Recent neonatal resuscitation guidelines suggest that sustained inflation may be considered in individual clinical circumstances or research settings.