Glycerol Phenylbutyrate Treatment of 2 Patients With Monocarboxylate Transporter 8 Deficiency.

Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency.

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

Unlabelled: To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after.

Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.

Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development.

Novel Calcium-Sensing Receptor (CASR) Mutation in a Family with Autosomal Dominant Hypocalcemia Type 1 (ADH1): Genetic Study over Three Generations and Clinical Characteristics.

Introduction: Activating mutation of the calcium-sensing receptor gene (CASR) reduces parathyroid hormone secretion and renal tubular reabsorption of calcium, defined as autosomal dominant hypocalcemia type 1 (ADH1). Patients with ADH1 may present with hypocalcemia-induced seizures. Calcitriol and calcium supplementation in symptomatic patients may exacerbate hypercalciuria, leading to nephrocalcinosis, nephrolithiasis, and compromised renal function.

Alarming increase in ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the first wave of the COVID-19 pandemic in Israel.

Objective: To evaluate the incidence and severity of ketoacidosis (DKA) at type 1 diabetes diagnosis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Israel.

Research Design And Methods: A population-based study the product of a national collaboration of Israeli pediatric diabetes centers investigated the presentation of childhood-onset type 1 diabetes. The frequencies of DKA and severe DKA observed during the COVID-19 period from March 15, 2020 (commencement of the first nationwide lockdown) until June 30, 2020 were compared with the same periods in 2019, 2018, and 2017 using multivariable logistic regression, adjusting for age, sex, and socioeconomic position.

Reproducibility and Refinement of Urinary LH in the Screening of Progressive Puberty in Girls.

Context: First-voided urinary LH (FVU-LH) has been suggested as an alternative to GnRH stimulation test for detection of precocious puberty.

Objective: To evaluate the reproducibility of FVU-LH, its correlation with basal and GnRH-stimulated gonadotropins, and its diagnostic value for differentiating progressive from nonprogressive puberty.

Design And Participants: Clinical and endocrine data were obtained from the medical records of 95 girls with suspected progressive puberty who underwent 2 consecutive FVU-LH tests.

Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature.

Objectives Recommendations for vitamin D (VitD) intake and target serum levels of 25(OH)D in preterm infants are diverse. We hypothesized that preterm infants with low birth weight (BW) have low dietary intake of VitD and therefore should be supplemented with higher amounts of VitD. Methods Infants with BW < 2 kg were supplemented with 600 units of VitD a day during the first 2-6 weeks of life, whereas infants with BW>2 kg continued with the routine supplementation of 400 units of VitD daily.

Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study.

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.

Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally.

Birth during the moderate weather seasons is associated with early onset of type 1 diabetes in the Mediterranean area.

Aim: To assess the association of seasonal and perinatal parameters with early age of type 1 diabetes (T1D) onset.

Methods: A cross-sectional review of all medical records of T1D patients born between the years 1990 and 2005, and diagnosed before/by the age of 10 years, from 13 university-affiliated paediatric medical centres in Israel, was performed. Data included: gender, ethnicity, seasons of birth and disease onset, birth gestational age and weight, and autoimmune diseases of the probands and their first-degree family members.

The natural history of congenital hypothyroidism with delayed TSH elevation in neonatal intensive care newborns.

Objective: To assess the clinical and neurological outcomes in newborns with primary congenital hypothyroidism presented with delayed TSH elevation (dTSH), and to define parameters that may predict the evolution of transient vs. permanent hypothyroidism in these newborns.

Design And Patients: An observational study was performed of a cohort of 113 children with a history of dTSH.

De Novo Mutations in Affecting eIF2 Signaling Cause Neonatal/Early-Onset Diabetes and Transient Hepatic Dysfunction.

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants.

Combined Gestational Age- and Birth Weight-Adjusted Cutoffs for Newborn Screening of Congenital Adrenal Hyperplasia.

Context: Congenital adrenal hyperplasia (CAH) was among the first genetic disorders included in newborn screening (NBS) programs worldwide, based on 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots. However, the success of NBS for CAH is hampered by high false positive (FP) rates, especially in preterm and low-birthweight infants.

Objective: To establish a set of cutoff values adjusting for both gestational age (GA) and birthweight (BW), with the aim of reducing FP rates.

Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors.

The aim of the study was to assess the epidemiology and risk factors of adrenal crises (AC) in children with adrenal insufficiency (AI). Children diagnosed with AI between 1990 and 2017 at four Israeli pediatric endocrinology units were studied. Demographic and clinical data were retrieved retrospectively from their files.

Prevalence of early and late prematurity is similar among pediatric type 1 diabetes patients and the general population.

Background: The incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades, as has the incidence of preterm births (<37 weeks). We aimed to evaluate and compare the prevalence of prematurity and early prematurity (<34 weeks) and birth season variability among T1DM and non-T1DM children.

Methods: A nationwide cross-sectional study was conducted, with linkage of data from 13 paediatric diabetes centers and Israeli National Registries, including T1DM patients and general non-T1DM population, born during 2000 to 2013.

The proportion of familial cases of type 1 diabetes is increasing simultaneously with the disease incidence: Eighteen years of the Israeli Pediatric Diabetes Registry.

Background: The global rise in incidence of type 1 diabetes (T1D) is too rapid to be attributed to susceptible genetic background, pinpointing a significant role for environmental factors. Unlike the theory that the need for genetic susceptibility has lessened over time, we hypothesized that the rise in T1D incidence is faster in a genetically susceptible population.

Subjects And Methods: The study population comprised of 5080 patients aged 0 to 17 years who were reported to the National Israel Diabetes Registry between 1997 and 2014.

Risk Factors for the Development of Delayed TSH Elevation in Neonatal Intensive Care Unit Newborns.

Context: Delayed thyrotropin (TSH) elevation (dTSH) is defined as elevated TSH at the second neonatal screening (after normal TSH levels at the initial screening) in premature, low-birth-weight, and ill newborns, mostly in the neonatal intensive care unit (NICU) setting. The pathogenesis of dTSH is elusive.

Objective: To identify the risk factors for dTSH development among newborns in the NICU.

Characteristics of Delayed Thyroid Stimulating Hormone Elevation in Neonatal Intensive Care Unit Newborns.

Objectives: To elucidate the incidence, clinical characteristics, and short-term outcome of delayed thyroid stimulating hormone (TSH) elevation (dTSH) in a large cohort of newborns admitted to the neonatal intensive care unit.

Study Design: Data were gathered from a cohort of 13 201 newborns admitted to the neonatal intensive care unit born between January 1, 2008, and October 31, 2014, who underwent TSH measurements because of low T4 levels on the second screen. The data from the newborn screening program included gestational age, birth weight (BW), T4 levels, and short-term outcome.

Homozygous deletion of TRMT10A as part of a contiguous gene deletion in a syndrome of failure to thrive, delayed puberty, intellectual disability and diabetes mellitus.

Two recent reports describe a new syndrome of intellectual disability, short stature, microcephaly, and young onset diabetes or disturbed glucose metabolism in association with inactivating mutations in the TRMT10A gene. We investigated the clinical spectrum presented by a 17-year-old female with a homozygous contiguous gene deletion involving the TRMT10A gene. From infancy, she presented with failure to thrive and microcephaly.

Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods.

Aim: The objective of this study was to validate basal, post-gonadotropin-releasing hormone analogue (post-GnRHa) and first-voided urinary LH (ULH) as alternatives to an LHRH stimulation test in monitoring treatment efficacy in central precocious puberty (CPP).

Methods: Seventeen girls with CPP were followed over 22.5±9.

The diagnostic value of first-voided urinary LH compared with GNRH-stimulated gonadotropins in differentiating slowly progressive from rapidly progressive precocious puberty in girls.

Objective: Characterization of pubertal progression is required to prevent unnecessary intervention in unsustained or slowly progressive (SP) precocious puberty (PP), while delivering hormonal suppression in rapidly progressive (RP) PP. We aimed to assess the diagnostic value of first-voided urinary LH (ULH) compared with GNRH-stimulated gonadotropins in differentiating these forms of PP.

Methods: A total of 62 girls with PP underwent both GNRH stimulation and ULH assay.

Neonatal hyperthyrotropinemia is associated with low birth weight: a twin study.

Objective: Contradictory reports ascribe neonatal hyperthyrotropinemia (HT) to prematurity or small weight for gestational age. We aimed to evaluate the association between neonatal HT and birth weight (BW), recovery rate of the disorder, and possible association with perinatal stress.

Design: Based on a neonatal screening database, a retrospective twin study was designed where within-pair differences in thyroid function were evaluated while controlling for differences in gestational age and thyroid-affecting environmental confounders.

Lack of association between seroconversion and catch-up growth in children with celiac disease.

Objective: To assess the association between seroconversion and catch-up growth during the first year of a gluten-free diet (GFD) program in children with celiac disease (CD).

Methods: All prepubertal and biopsy-proven children diagnosed with CD between January 1999 and August 2009 were included in a retrospective study (n=55). Growth parameters and celiac antibodies were documented before and after 6 (period 1) and 12 months (period 2) of GFD, respectively.