Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.

BACKGROUND: Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. OBJECTIVE: To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. METHODS: We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild-type ELANE/G6PC3 were referred for next-generation sequencing. RESULTS: Sixty-five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman-Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte-colony stimulating factor or due to myeloid transformation. CONCLUSIONS: The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow-up.

The effect of COVID-19 pandemic on hospitalizations and disease characteristics of adolescents with anorexia nervosa.

Social distancing and quarantines have major negative psychological implications. Our aim was to study the rate of pediatric hospitalizations due to anorexia nervosa (AN) during the first year of coronavirus disease 2019 (COVID-19) pandemic as compared to previous years, with regard to clinical and laboratory parameters. This is a retrospective study in a tertiary pediatric hospital in Israel. Data regarding inpatient hospitalizations due to AN were retrieved, then epidemiological, clinical, and laboratory parameters compared. During the entire study period, 275 hospitalizations were due to AN: 94 patients were admitted during the 12 months of the pandemic as compared to a yearly mean of 45.25 during 2015-2019, resulting in a 2.4-fold increase (p < 0.001). The mean admission age and female predominance were similar in the two study groups. The weight of the patients at admission was higher during the COVID-19 period (44.5 kg vs. 41.2 kg, p = 0.004), and fewer patients had clinical signs typical of AN upon physical examination (p = 0.022). There was a 35% reduction in median hospitalization duration (9 days [IQR 8.21] in 2020-2021 and 14 [IQR 6, 16.75] days in 2015-2019, p = 0.01). No other differences were found. CONCLUSIONS: During the first year of the COVID-19 pandemic, there was a significant increase in the number of adolescents hospitalized with AN. Nevertheless, disease characteristics were not more severe as compared to the preceding 5 years. WHAT IS KNOWN: • Social distancing and quarantines were announced during the COVID-19 pandemic in numerous countries. These measures have potential negative psychological effects on adolescents. WHAT IS NEW: • During the COVID-19 pandemic period, there was an increase in the number of hospitalizations of adolescents with AN, although disease characteristics were not more severe as compared to the preceding 5 years.