ESPE Yearbook of Paediatric Endocrinology

Brief summary: This translational study evaluated mRNA expression of hypothalamic neuroglial markers in two transgenic mice with either enhanced or reduced consensual GH-IGF-1 signaling and in Hepatocyte-specific GH receptor (GHR) knockout male mice, with high GH circulating-levels and low IGF-1 concentrations. The study demonstrated a direct action of GH on neuroinflammation, independently of IGF-1 levels.Although the brain is not considered a classical...

Brief summary: A four centre prospective longitudinal study of 315 transgender and non-binary adolescents in the USA showed improvement in gender congruence and appearance and some reduction of depression and anxiety (but not in birth-registered males) after 2 years of gender affirming hormone (GAH) treatment.The race is on to provide clear evidence to support hormonal intervention for transgender adolescents. This longitudinal study employed a number of...

Brief Summary: This prospective singleton birth cohort (N=288, 43.4% male) from Flanders, Belgium, was a subset of a larger longitudinal cohort (ENVIRONAGE). The authors used a targeted proteomic panel to measure 386 inflammatory-related proteins in cord blood and examined their associations with birth weight (BW), birth weight ratio (BWR - BW divided by the median BW for gestational age for sex and parity), and rapid infant weight gain (defined as [weight z score at 12 m minu...

Brief Summary: This study assessed the effect of growth hormone (GH) on WIP1 (wild-type p53-inducible phosphatase 1), a key mediator of the DNA damage response (DDR). GH suppressed DDR by inducing WIP1, which dephosphorylates and inactivates ATM (ataxia-telangiectasia mutated) kinase and its downstream effectors (such as CHK2, p53 and H2AX), leading to the accumulation of unrepaired DNA, which can potentially contribute to tumorigenesis.This elegant stud...

In brief: This article describes the functionalities of the Global ALPL gene variant classification project, which aims to reclassify variants of uncertain significance (VUS) in the ALPL gene and to continuously assess and update genetic, phenotypic, and functional variant information in hypophosphatasia.Commentary: Hypophosphatasia (HPP) is a rare genetic disorder caused by loss-of-function mutations in the alkaline phosphatase ( A...

In brief: This multinational, randomised, double-blind, placebo-controlled, Phase 2 study examined the safety and efficacy of vosoritide, a recombinant C-type natriuretic peptide (CNP) analogue, in 75 children with achondroplasia under age 5 years. Mean gain in height Z-score after 52-weeks was 0•25 (95% CI -0•02 to 0•53). The study was sponsored by BioMarin Pharmaceutical.Commentary: Achondroplasia is one of the most common constitutional...

Brief Summary: This molecular study explored the role of microRNAs (miRNAs) in mammalian sex determination. It used bulk and single-cell RNA-seq (scRNA-seq) alongside time-course expression analyses in a knockout mouse model to assess the role of the miR-17~92 cluster in this process.miRNAs are small, single-stranded, non-coding RNA molecules, 21 to 23 nucleotides in length, that mediate post-transcriptional gene regulation. Hurtado A et al. d...

Brief Summary:This study using mice and human models, shows that human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert biliary corticoids into progestins through 21-dehydroxylation. It thereby shows that a class of immuno- and metabo-regulatory steroids are transformed into a class of sex hormones and neurosteroids. It also illustrates that gut hydrogen gas production is essential and sufficient to support this metabolic pathway, which is m...

Lancet Diabetes Endocrinol. 2020;8(8):683–692. doi: 10.1016/S2213-8587(20)30163-7. PMID: 32707116SAGhE is a large independent European consortium including eight different countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK) which was set up to evaluate the long-term safety of rhGH in a large cohort (>24 000) of young adult patients t...

Proc Natl Acad Sci USA. 2020 Jun 16;117(24):13680–13688. 10.1073/pnas.1921676117. PMID: 32493750.On the search for a genetic cause for 46,XX virilization due to testicular (TDSD) or ovotesticular DSD (OTDSD), 78 individuals were studied by whole exome sequencing. In 7 cases, heterozygous de novo variants were found in the 4th zinc finger (ZF4) of the Wilms tumor 1 gene (<em...