Differential Serum Phosphate Levels in Pediatric Febrile Syndromes and Their Clinical Significance.

BACKGROUND: The potential of hypophosphatemia (HP) to differentiate between febrile syndromes and its clinical significance in children without sepsis were not previously described. METHODS: Data were retrospectively collected of febrile children aged 3 months to 18 years, hospitalized at general pediatric wards during 2010-2019. Phosphate levels were compared between bacterial infection (BI), viral infection (VI), and Kawasaki disease (KD). Regression analyses were used to evaluate the relationship between HP and outcome. RESULTS: Of 3963 febrile children, 559 had BI, 3271 had VI, and 133 had KD. In BI compared to VI and KD, HP was more prevalent (49.2%, 19.7%, and 31.6%, respectively; P<0.001) and more severe [median (interquartile range) phosphate standard deviation score: -1.85 (2.08), -0.56 (2.08), and -1.20 (2.28), respectively; P<0.001]. In the BI group, Pi-SDS level was lower among patients with than without bacteremia (-2.33 ± 1.8 vs. -0.79 ± 1.68; P<0.001). Phosphate levels displayed discriminatory potential between bacterial and viral etiologies, with an area under the curve of 0.719 (95% CI, 0.697-0.742). Minimal phosphate standard deviation score values had a negative weak correlation with the maximal C-reactive protein levels and white blood cell count. Univariate and multivariate analyses showed an association of HP with a more severe disease course, manifested by longer hospital stay [+2.10 (95% CI, 0.75-3.46) days; P=0.003] and a higher rate of intensive care unit admission [odds ratio, 2.63 (95% CI, 1.94-3.56); P<0.001). CONCLUSIONS: Hypophosphatemia rates were highest in bacterial etiology, intermediate in KD, and lowest in viral etiology and were associated with poorer outcomes. Phosphate level may serve as a marker for ruling out a bacterial etiology.

Apparent mineralocorticoid excess in Israel: a case series and literature review.

BACKGROUND AND OBJECTIVE: Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature. DESIGN: Retrospective cohort study. METHODS: Clinical, laboratory, and molecular data from patients' records were collected. RESULTS: Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while 2 patients presented during late childhood with CKD. Molecular analysis revealed 2 novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only 1 showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those 5 patients who presented early exhibited normal eGFR and near-normal blood pressure, but 2 have hypertension complications. The 2 patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation. CONCLUSIONS: In this 11-year follow-up report of 2 Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment.

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.