ENPP1 homozygous stop-loss variant causing generalized arterial calcifications of infancy: About a severe neonatal clinical case.

Generalized Arterial Calcifications of Infancy (GACI) is an extremely rare autosomal recessive genetic condition, mostly due to pathogenic variations in the ENPP1 gene (GACI1, MIM #208000, ENPP1, MIM #173335). To date 46 likely pathogenic or pathogenic distinct variations in ENPP1 have been described, including nonsense, frameshift, missense, splicing variations, and large deletions. Here we report a case of GACI in a male newborn with a homozygous stop-loss variant in ENPP1 treated in Nancy Regional University Maternity Hospital. Based on proband main clinical signs, clinical exome sequencing was performed and showed a deletion of one nucleotide leading to frameshift and stop-loss (NM_006208.3 (ENPP1):c.2746del,p.(Thr916Hisfs*23)). Clinical presentation is characterized by primary neonatal arterial hypertension resulting in hypertrophic cardiomyopathy decompensated by three cardiogenic shocks and a neonatal deep right sylvian stroke. The child died at 24 days of life. This is the first report of a pathogenic stop-loss variant in ENPP1. It is an opportunity to remind clinicians of GACI disease, a rare and severe etiology in neonates with severe hypertension, and possibility of bisphosphonates therapy.

[Value of gastric fluid to start antibiotics in premature babies suspected of having early neonatal bacterial infection]. / Intérêt du liquide gastrique dans la décision d'antibiothérapie du nouveau-né prématuré suspect d'infection bactérienne précoce.

The objective of this study was to evaluate the value of direct examination and culture of gastric fluid in the treatment of early neonatal bacterial infections (INBP) in pre-term infants. MATERIALS AND METHODS: Observational study conducted over 6 months in a Type III center. All hospitalized premature babies who had routine gastric fluid sampling at birth during the period of the study were included. They were classified into two groups: premature infants with probable or suspected infection and treated as such (Group 1) and premature infants with no infection or only having colonization (Group 2). RESULTS AND DISCUSSION: In total, 255 pre-term infants were included in the study. Group 1 consisted of 127 newborns and group 2 consisted of 128 newborns. The direct gastric fluid examination was positive in 51 newborns in Group 1 and in 46 newborns in group 2. The culture was positive in 25 newborns in group 1 and eight newborns in group 2. Direct examination of gastric fluid of the 255 children studied had low sensitivity (40.1%) and low specificity (64%) of INBP, with 52.6% positive predictive value (PPV) and 51.8% negative predictive value (NPV). The gastric fluid culture was specific (93.7%) of the INBP, sensitivity was low (19.6%), with PPV at 75.7% and NPV at 54%. CONCLUSION: These results undermine the relevance of the direct examination of gastric fluid in the delicate diagnosis of INBP. This direct examination has a low PPV and NPV. It is advisable not to start or stop antibiotic therapy solely on this argument; however, it can guide the choice of antibiotic therapy and remains useful for this reason. The culture of gastric fluid has very good specificity (93.7%).

[Neonatal therapeutic hypothermia: amplitude-integrated electroencephalography to confirm the indication]. / Hypothermie thérapeutique contrôlée pour asphyxie périnatale : intérêt de l'électroencéphalogramme d'amplitude pour évaluer l'indication.

Moderate hypothermia therapy (HT) after perinatal asphyxia of the newborn has clearly demonstrated its efficacy in reducing both mortality and long-term neurosensory sequelae. HT has now been introduced in many developed countries as a standard of care for term infants meeting the entry criteria for therapeutic cooling. However, this new therapy is only effective in case of an acute perinatal hypoxic-ischemic event. Since a number of potentially deleterious complications have been described during cooling, a strict evaluation of the newborn's status is mandatory. To help clinicians reliably select newborns who may benefit from HT, amplitude-integrated electroencephalography (aEEG) is today strongly recommended. The indication criteria for cooling include aEEG in addition to delivery history, Apgar score, cord pH and lactates, and neurological scoring for encephalopathy. We report a clinical case of a term baby girl, considered for HT in our unit, because of a clinical feature of severe neonatal encephalopathy, metabolic acidosis on cord pH, and a history of fetal distress on fetal heart rate monitoring. However, despite all these criteria, her early aEEG, like her classic EEG, showed no signs of hypoxic-ischemic encephalopathy (HIE). She was then denied HT and her early magnetic resonance imaging (MRI) exam showed no signs of HIE but typical features of a metabolic disorder (Zellweger-like syndrome). Thanks to the HT strict protocols, including early aEEG and MRI exam, the right diagnosis was rapidly made and the hypothesis of a hypoxic-ischemic event during delivery was finally ruled out.