ESPE Yearbook of Paediatric Endocrinology

Nature. 2021 volume 594, 398–402https://www.nature.com/articles/s41586-021-03552-wThe authors report a large genome-wide association study (GWAS) of type 1 diabetes (T1D) in 18 942 cases and 501 638 controls, finding 92 T1D-associated genomic loci (59 known and 33 novel). Furthermore they analyse DNA chromatin patterns in pancreas and peripheral white blood cells to help ident...

N Engl J Med. 2022 May 19;386(20):1877–1888. doi: 10.1056/NEJMoa2109191.Brief summary: This prospective cohort study leveraged data from the International Childhood Cardiovascular Cohorts (i3C) Consortium, including 42 324 participants at baseline and followed-up over a mean of 35 years, in order to investigate associations between cardiovascular risk factors (CVRF, including body-mass ind...

To read the full abstract: J Bone Miner Res 2018;33(7):1260-1271Osteogenesis imperfecta (OI) is characterized by early-onset skeletal fragility, often short stature, blue sclerae and some other features. OI is caused by mutations in the two genes encoding type I collagen, namely COL1A1 and COL1A2. Some previous reports have indicated that when the mutation involves the C-propeptide cleavage site in e...

To read the full abstract: JCEM 2017,102(11):4226-4234It has been recently demonstrated that activation of brown adipose tissue (BAT) in humans improves glucose homeostasis and insulin sensitivity and is associated with accelerated lipid metabolism (3, 4), suggesting BAT activation as an option not only for obesity prevention, but also in diabetes management. There is recent evidence that cold ex...

Brief summary: The authors provide the first description of antagonistic hormone mutations as the cause of congenital disease in humans. The paper describes detailed characterizations of two novel, antagonistic leptin mutations underlying a formerly unrecognized form of congenital leptin dysfunction and delineate the challenges these mutations pose to the diagnosis and therapy of the disease.After the initial description of biologically inactive leptin v...

J Clin Endocrinol Metab. 2021 May 13;106(6):1728–1741. doi: 10.1210/clinem/dgab080. PMID: 33571362This report gathered data from two large observational studies (NordiNet International Outcome Study and ANSWER Program) aimed at assessing the incidence of adverse drug reactions (ADRs), serious adverse events (SAEs), and their relation with rhGH dose. The whole study cohort included 37,7...

J Bone Miner Res. 2021 Aug;36(8):1594-1604.Abstract: https://pubmed-ncbi-nlm-nih-gov/33900645/In Brief: Enzyme replacement therapy with human ENPP1-Fc protein in Enpp1asj/asj mice, a murine model of ENPP1 deficiency, restored circulating levels of PPi, prevented clinical manifestations and decreased mortality.Commentary: ENPP1 deficiency causes gen...

To read the full abstract: Sci Rep 2017; 22(7):12225The GH/IGF1 axis has historically been considered the most relevant regulator of growth. However, defects in the GH/IGF1 axis can be identified only in a minority of children with short stature. Human growth is dependent on chondrocyte proliferation and hypertrophy as well as structure and function of extracellular matrix in the gro...

Brief summary: In this large-scale, multicenter DNA sequencing study, probands (and families; n=13 449) with previously undiagnosed, severe, likely monogenic, complex developmental disorders from 24 centers in the UK and Irland were studied by whole exome sequencing and microarray analysis. Multimodal data analysis yielded a diagnosis in 41%, more likely with TRIO family analysis. Probands with a history of extreme prematurity, in utero exposure to antiepileptics and ...

Brief Summary: This study explored the relationship between Somatostatin Receptor 2 (SSTR2) immunoreactivity and succinate dehydrogenase complex iron sulfur subunit B (SDHB) immunoreactivity, mutational status, and clinical behavior of paragangliomas (PPGLs), and evaluated SSTR-based therapies in metastatic PPGLs. The findings highlight SSTR2 expression as a novel biomarker for metastatic behavior in PCC, PGL and SDHB/ SDHx mutations. They also suggest that SSTR-based therapie...