Impact of stopping burosumab treatment at the end of skeletal growth in adolescents with X-linked hypophosphatemia (XLH).

Many adolescents with X-linked hypophosphatemia (XLH) currently have to stop treatment with burosumab at the end of skeletal growth. We describe the experience of a cohort of adolescents with XLH before, during, and after stopping burosumab (median treatment duration 37.5 months).

Preservation of fat mass at the expense of lean mass in children with end-stage chronic liver disease.

Background: Sarcopenia predicts morbidity and mortality in end-stage chronic liver disease (ESCLD). Here, we describe changes in body composition in children with ESCLD before and after liver transplantation (LT).

Methods: Retrospective analysis of whole body DXA scans performed before and after LT over 4 years.

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses.

Paediatric Society and Hyperinsulinism Charity National Surveys on CGM Access for Patients With Recurrent Hypoglycaemia.

Context: Recurrent hypoglycemia can result in significant neurological impairments in children and continuous glucose monitoring (CGM) technology has been shown to reduce recurrent hypoglycemia in conditions such as type 1 diabetes. In the United Kingdom, CGM devices are currently only recommended by the National Institute of Clinical Excellence (NICE) for patients with diabetes and not for other diagnoses.

Objective: To examine access to CGM technology for children and young people with recurrent hypoglycemia in the United Kingdom.

Discharge outcome analysis of 1089 transgender young people referred to paediatric endocrine clinics in England 2008-2021.

Introduction: The destination of transgender and gender variant young people referred by the National Health Service (NHS) Gender Identity Development Service (GIDS) to, and discharged from the two English paediatric endocrine liaison clinics is not known.

Methods: 1151 young people referred after full assessment by the GIDS; 827 to University College London Hospital since 2008; 324 to Leeds Children's Hospital since 2013. Discharge categorisation was by agreed criteria.

Genetic Characterization of Short Stature Patients With Overlapping Features of Growth Hormone Insensitivity Syndromes.

Context: Growth hormone insensitivity (GHI) in children is characterized by short stature, functional insulin-like growth factor (IGF)-I deficiency, and normal or elevated serum growth hormone (GH) concentrations. The clinical and genetic etiology of GHI is expanding.

Objective: We undertook genetic characterization of short stature patients referred with suspected GHI and features which overlapped with known GH-IGF-I axis defects.

Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021).

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion.

Homozygosity for the pathogenic RET hotspot variant p.Cys634Trp: A consanguineous family with MEN2A.

Multiple endocrine neoplasia type 2 (MEN2) is a dominantly inherited condition with defined correlations between the genetic variant and clinical presentations. The location of pathogenic variants in the RET gene is a significant determinant of disease presentation and is associated with variable gene activation. Heterozygous pathogenic variants in codon 634 result in earlier onset of medullary thyroid carcinoma and higher incidence of phaeochromocytoma.

How to interpret IGF-1 and growth hormone stimulation tests.

You are seeing an 11-year-old boy in a general paediatric clinic referred with short stature. His height is below the 0.4th centile.

GHR gene transcript heterogeneity may explain phenotypic variability in GHR pseudoexon (6Ψ) patients.

Objectives: The homozygous GH receptor (GHR) pseudoexon (6Ψ) mutation leads to growth hormone insensitivity (GHI) with clinical and biochemical heterogeneity. We investigated whether transcript heterogeneity (6Ψ-GHR to WT-GHR transcript ratio) and/or concurrent defects in other short stature (SS) genes contribute to this.

Methods: 6Ψ-GHR and WT-GHR mRNA transcripts of 4 6Ψ patient (height SDS -4.

Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389.

Congenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are important as they inform health care planning and can aid interpretation of genetic testing results when assessing the frequency of variants in large-scale, unselected sequencing databases. Whilst minimal incidence rates have been calculated for four European countries, the incidence of CHI in the UK is not known.

Phenotypic diversity and correlation with the genotypes of pseudohypoaldosteronism type 1.

Background Type I pseudohypoaldosteronism (PHA1) is a rare condition characterised by profound salt wasting, hyperkalaemia and metabolic acidosis due to renal tubular resistance to aldosterone (PHA1a) or defective sodium epithelial channels (PHA1b or systemic PHA). Our aim was to review the clinical presentation related to the genotype in patients with PHA1. Methods A questionnaire-based cross-sectional survey was undertaken through the British Society of Paediatric Endocrinology and Diabetes (BSPED) examining the clinical presentation and management of patients with genetically confirmed PHA1.

Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation.

Background: Patients with homozygous intronic pseudoexon GH receptor () mutations (6Ψ) have growth hormone insensitivity (GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 6Ψ patients and their responses to rhIGF1 therapy.

Methods: 20 patients (12 males, 11 families, mean age 4.

Diagnostic conundrums in antenatal presentation of a skeletal dysplasia with description of a heterozygous C-propeptide mutation in COL1A1 associated with a severe presentation of osteogenesis imperfecta.

Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies.

Fifteen-minute consultation: The child with short stature.

Short stature can be a cause of distress for children and families. It is not usually pathological, but it is important to identify treatable conditions. This article presents a systematic approach to the evaluation of a child with short stature, covering differential diagnoses, first line investigations and indications for treatment with growth hormone.

Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency.

Context: It is estimated that 3-30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics.

Patients And Methods: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR.

IGF-I signalling in bone growth: inhibitory actions of dexamethasone and IL-1beta.

Objective: To determine if glucocorticoids and proinflammatory cytokines inhibit bone growth through a common mechanism involving impaired IGF-I signalling.

Design: IGF-I (100 ng/ml), dexamethasone (dex) (10(-6)M) and IL-1beta (10 ng/ml) with inhibitors of the PI3K (LY294002) and Erk 1/2 (PD98059 and UO126) IGF-I pathways (all 10 microM) were studied using the ATDC5 chondrocyte cell line and murine fetal metatarsal cultures.

Results: IGF-I stimulated ATDC5 chondrocyte proliferation (322%; P < 0.