ESPE Abstracts

Objective: This project aims to evaluate the effect of two isotopically labelled internal standards on the quantification of 17OHP by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) as an orthogonal technique.Methods: Three LC-MS/MS and one GC-MS/MS laboratories, spanning four countries worldwide, who routinely measure serum17OHP, compared two internal ...

Background: The aetiology of congenital hypopituitarism (CH) is unknown in the majority of patients. In our cohort of 200 cases, it was possible to establish the genetic cause in only 13 patients (6.5%). Copy number variants (CNVs) have been implicated as the cause of genetic syndromes with previously unknown aetiology.Objective: To study the presence of CNVs and its relevance in patients with CH of unknown cause associated with complex phenotypes.<p...

Background: Disproportional short stature (DSS) is the most frequent clinical presentation of skeletal dysplasias, which are a heterogeneous group of more than 450 disorders of bone. Skeletal survey is important to establish the diagnosis and to guide the genetic test, but has several limitations, especially in mild and atypical cases.Objective and hypotheses: To identify the genetic aetiology of DSS by exome sequencing.Method: Who...

Background: Patients with autosomal dominant hypocalcemia type 1 (ADH1), due to germline gain-of-function calcium-sensing receptor (CASR) mutations, have hypocalcemia and seizures, hyperphosphatemia, hypercalciuria and inappropriately low parathyroid hormone (PTH) concentrations. Treatment for ADH1 comprises calcium and vitamin D analogs, however, their use predisposes to nephrocalcinosis and renal impairment. In contrast, recombinant human PTH(1-34) may incre...

Introduction: Previous studies showed that non-obese children and adults with Prader-Willi syndrome (PWS) have a low frequency of metabolic syndrome (MetS), while obese ones have a frequency similar to that of non-PWS obese. It is known that individuals born small for gestational age (SGA) have a greater predisposition to the development of MetS. Recent neonatal percentiles of subjects with PWS (Salvatoni et al, Am J Med Genet Part A, 2019) documented...

Context: The traditional approach to childhood obesity management is lifestyle modification/LSM. Nevertheless, the response rate is variable and difficult to predict.Aim: A systematic search for markers to predict outcomes of simple LSM in pediatric obesity management.Patients/Methods: Out of 240 children with obesity (BMI>97%), recruited to a prospective ‘multi-OMICS’ study granted b...

21-hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH) and is caused by mutations in the CYP21A2 gene. 21OHD causes a wide array of clinical symptoms that result from gluco- and mineralocorticoid deficiency and adrenal androgen excess. In most cases, supra-physiological glucocorticoid doses are necessary which may cause short stature, obesity, hypertension, cardiovascular and metabolic co-morbidity with reduced quality of lif...

Background and hypothesis: Mitochondrial disorders are multisystemic conditions associated with sensorineural hearing loss, encephalomyopathy, lactic acidosis, and non-autoimmune diabetes. The majority of molecular etiologies involve mutations in the genes encoding the oxidative phosphorylation system's components. Superoxide generation is significantly increased and causes oxidative damage in the affected tissues in these disorders. The establishment of ...

In a randomized open-label phase 3 trial in 62 children (1–12 years) with X-linked hypophosphatemia (XLH) (NCT 02915705), switching from conventional therapy (oral phosphate plus active vitamin D) to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved serum phosphate concentration, rickets, lower-extremity deformities, growth, mobility, and patient-reported outcomes (PROs) at 64 weeks. Children in Europe, USA, Canada, and Australia wh...

Children diagnosed with adrenocortical tumors (ACT) have variable prognosis depending on disease presentation at diagnosis. Available therapeutic options render excellent outcome for a subset of patients, but limited improvement in the survival of those diagnosed with non-localized/advanced disease. ACT DNA methylation was recently demonstrated to be a robust and independent prognostic biomarker. Aiming to identify potential therapeutic targets for these children, we compared ...