The invaluable role of consanguinity in providing insight into paediatric endocrine conditions: Lessons learned from congenital hyperinsulinism, monogenic diabetes, and short stature

Consanguineous families have often played a role in the discovery of novel genes, especially in paediatric endocrinology. At this time, it has been estimated that over 8.5% of all children worldwide have consanguineous parents. Consanguinity is linked to demographic, cultural and religious practises and is more common in some areas around the world than others. In children with endocrine conditions from consanguineous families, there is a greater probability that a single gene condition with autosomal recessive inheritance is causative. From 1966 and the first description of Laron syndrome, through the discovery of the first KATP channel genes ABCC8 and KCNJ11 causing congenital hyperinsulinism in the 1990s, to recent discoveries of mutations in YIPF5 as the first cause of monogenic diabetes due to the disruption of the endoplasmic reticulum (ER)-to-Golgi trafficking in the β-cell and increased ER stress; positive genetic findings in children from consanguinity have been important in elucidating novel genes and mechanisms of disease, thereby expanding knowledge into disease pathophysiology. The aim of this narrative review is to shed light on the lessons learned from consanguineous pedigrees with the help of three fundamental endocrine conditions that represent an evolving spectrum of pathophysiological complexity – from congenital hyperinsulinism, a typically single cell condition, to monogenic diabetes which presents with uniform biochemical parameters (hyperglycaemia and glycosuria), despite varying aetiologies, up to the genetic regulation of human growth – the most complex developmental phenomenon.

Paediatric endocrinology

This chapter covers paediatric endocrinology. It starts with normal growth, then goes on to short stature, and constitutional delay of growth and puberty. Primary and secondary growth hormone deficiency are then explained, and treatment is outlined alongside GH resistance. It goes on to hypothyroidism, coeliac disease, skeletal dysplasias, and Turner syndrome. Small gestational age, and tall stature and rapid growth are all covered, alongside normal puberty, precocious puberty, and delayed or absent puberty. Normal sexual differentiation and disorders of sexual development and the assessment of ambiguous genitalia are included.

Levels of physical activity and barriers to sport participation in young people with gender dysphoria

Objectives To determine the levels of physical activity (PA) in young people with gender dysphoria (GD) and help identify factors which deter participation. Methods Fifty-six young people who attended paediatric endocrinology because of GD, June to October 2019, and were on treatment with gonadotrophin-releasing hormone (GnRH) analogue were approached to participate in a survey. Results A total of 55 young people (98%) responded to the survey. Thirty-eight (69%) participated in PA for >1 h/week. Thirty-two (58%) reported high motivation level for exercise. Those had median age of 15.9 years (10.7, 18.7) at the time of survey, and 13.6 years (9.7, 17.6) at start of GnRH analogue compared to 16.7 years (13.9, 18.5) (p, 0.047) and 15.4 years (11.2, 18.0) (p, 0.009) of the 23 (42%) who reported low motivation. Forty-one (74.5%) reported barriers when accessing PA, such as not being as good as others (75%), revealing sports clothing (73%) and not satisfied with body image (47%). Those were older (16.4 years [10.9, 18.7] vs. 14.7 years [10.7, 18.4] [p, 0.011]) at the time of survey and at start of GnRH analogue (14.9 years [9.7, 18.0] vs. 12.5 years [10.6, 15.2] [p, 0.0001]) than those 14 (25.5%) who reported facing no barriers. Twelve (85.7%) of those reporting no barriers stated high motivation levels compared to 20 (48.8%) of those reporting barriers (p, 0.026). Conclusions Strategies aimed at improving participation are twofold: first to improve motivation, especially in post-pubertal young people, and secondly to achieve societal change to help eliminate barriers.

Peer Review of Paediatric Endocrine Services in the UK: A Template for Quality and Service Improvement

<b><i>Background:</i></b> Independent peer review of healthcare services can complement existing internal-, institutional-, and national-level regulatory mechanisms aimed at improving quality of healthcare. However, this has not been reported for paediatric endocrinology services in the UK. We aimed to test feasibility and acceptability through a first cycle of a national peer review of paediatric endocrine services. <b><i>Methods:</i></b> Tertiary centres in paediatric endocrinology across the UK were assessed against 54 quality standards, developed by the British Society for Paediatric Endocrinology and Diabetes (BSPED) in five domains of healthcare by a team comprising paediatric endocrinologists and specialist nurses. The evaluation was supported by a self-assessment. A post-peer-review questionnaire was used as feedback. <b><i>Results:</i></b> All 22 centres in the UK underwent independent peer review between 2011 and 2017. Each served a median population of 2.6 million (range 1–8 million) and offered 1,872 (range 779–6,738) outpatient consultations annually. A total of 43 (range 30–49) standards were met in combined evaluation of all centres. Variance of adherence for essential standards ranged from 52 to 97% at individual centres with 90% adherence demonstrated by 32% of centres. Post-review feedback showed 20/22 (95%) validating the utility of the peer review. <b><i>Conclusions:</i></b> The BSPED peer review of all UK centres providing paediatric endocrine services is shown to be feasible and provides a quality benchmark for replication by national services.

Perspectives of the European Society of Endocrinology (ESE) and the European Society of Paediatric Endocrinology (ESPE) on rare endocrine disease

Purpose Rare diseases affect <1 in 2000 people. Despite their rarity, they collectively affect ~30 million people across Europe. The aim of this article is to present the view of our European endocrine societies on the care of patients with rare endocrine conditions. Methods We evaluated the current situation of patients with rare endocrine disease and present the joint views of the European Society for Endocrinology (ESE) and the European Society for Pediatric Endocrinology (ESPE) on how the endocrine disciplines can support and contribute to a better health of patients with rare endocrine conditions in Europe. Results Rare diseases pose many challenges, including early diagnosis and innovative treatment options. Rare endocrine diseases can be found among inherited disorders, cancers, and conditions associated with metabolic disorders such as diabetes, calcium and bone metabolism, lipid metabolism, hypogonadism, and adrenal, pituitary, and thyroid dysfunction. According to the European Registries for Rare Endocrine conditions, there are over 440 distinct rare diseases that affect the endocrine system. Rare endocrine diseases are often chronic and life-threatening. Conclusions ESE and ESPE support a strategic plan to address unmet needs in the area of rare endocrine conditions. The EU should continue to evolve and expand its plans for funding European Reference Networks so that they can expand their activities.