ESPE Abstracts

Objectives: Abdominal fat has been strongly linked to increased cardiometabolic risk and impaired glucose regulation in adults. Owing to the lack of detailed body composition phenotyping in most previous child cohort studies, the temporal links between abdominal fat accumulation and impaired glucose regulation have not been well established. In this study, we evaluated the associations of abdominal fat assessed by MRI at early infancy (≤21 days after birth) and at 4.5 ye...

Context: Prenatal dexamethasone (Dex) therapy is used in female foetuses with congenital adrenal hyperplasia (CAH) to suppress adrenal androgen excess and prevent virilisation of the external genitalia. The prenatal dexamethasone dose of 20 µg/kg/d has been used for decades in prenatal CAH. Despite the risks for the treated mother and potentially for the unborn child, no clinical study or evaluation had been conducted in order to determine a Dex dose with a scientific rat...

Introduction: Prenatal dexamethasone (Dex) therapy in female fetuses with congenital adrenal hyperplasia (CAH) has been conducted for 40 years but the dose given to the pregnant woman has never been fully evaluated in a randomized clinical trial. Prenatal Dex therapy is associated with potential side effects for both mother and child.Methods: In a study funded by the German Federal Ministry of Education and Research (BMB...

Introduction: Genetic alterations within the cAMP/PKA pathway, including the genes GNAS, PDE11A, PDE8, PRKAR1A/B, and PRKACA, result in a spectrum of adrenocortical disorders. To date, somatic PRKACA variants and germline PRKACA copy number gain have been associated with the development of cortisol-secreting adrenocortical adenomas and bilateral adrenal hyperplasia, respectively. While variants within the PRKAR1A ge...

Background: Reaching a definitive diagnosis in individuals with XY DSD is challenging and the time taken to reach a diagnosis is an important clinical benchmark that has not been sufficiently explored in this group of conditions.Objective: To evaluate the diagnostic process with a focus on the time to diagnosis in children with XY DSD reported via the e-reporting platform (e-REC) of the European Registries for Rare Endoc...

Background: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and is predominantly caused by developmental abnormalities known as thyroid dysgenesis (TD). Several transcription factors have been described in its aetiology, but defects in the known genes only account for a small proportion of cases.Methods: To identify novel genes involved in TD, we performed exome sequencing in 7 unrelated ...

Background: Studying patients with rare Mendelian diabetes has highlighted molecular mechanisms regulating β-cell pathophysiology. Previous, experimental studies have shown that Class IIa histone deacetylases (HDAC4, 5, 7, and 9) modulate mammalian pancreatic endocrine cell differentiation, function and finally glucose homeostasis.Methods: We performed exome sequencing in one adolescent boy with non-autoimmune di...

Background: Mutations in genes involved in insulin secretion or regulation of β cell identity cause both persistent neonatal diabetes (PND) and hyperinsulinemic hypoglycemia of infancy (HHI) pinpointing shared pathogenic mechanisms. KCNQ1 encodes a potassium channel protein, Kv7.1, which is a voltage-gated potassium channel expressed in cardiac tissue, pancreas, inner ear neurons, and other tissues. Variants in or nearby to KCNQ1 were linked t...

Introduction: Congenital hyperinsulinism (CHI) is a group of rare endocrine disorders characterized by repeated episodes of hypoglycemia caused by an excessive insulin secretion from the pancreas beta cells. The etiopathogenesis, phenotype, treatment, and prognosis of individual CHI cases are variable and not completely described.Aims: To gather and describe clinical and genetic data about CHI cases diagnosed within the large EuRRECa net...

Introduction: The diagnosis and treatment of patients with rare diseases is often difficult as most clinicians do not encounter them. Therefore, centralization and collaboration between centers of expertise is necessary. European Reference Networks (ERN’s) such as RareEndoERN provide a platform for this, with one of its main thematic groups having a specific focus on rare growth and obesity disorders. Genetic obesity encompasses a heterogeneous group of c...