ESPE Abstracts

Nuclear Factor kappa B (NF-κB) is a group of seven transcription factors, including p65 (RelA), c-Rel, RelB, p50/p105 (NF-κB1), and p52/p100 (NF-κB2). Upon activation by a wide variety of stimuli, NF-κB translocates to the nucleus, where it modulates the expression of target genes involved in cell growth, survival, and death.Previous evidence indicates that NF-κB regulates bone growth and development. Mice deficient in both the N...

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. In the past 20+ years there have been tremendous advances in the understanding of the molecular genetics of HI, including the discovery of the mechanisms responsible for a focal form of the disease that can cured surgically. However, treatment options for non-focal HI continue to be limited, with only one drug currently approved for this indication. As a result of delay...

Introduction: Achondroplasia is the most common of the skeletal dysplasias and short stature with severe anatomic disproportion. Bone endochondrial growth is affected. The entity was described by Depaul in 1851 and the name which comes from the Greek word chondros (cartilage) and plasis (formation) was given by Parrot. It is an autosomal dominant monogenic disease with complete penetrance. Incidence is 1/25000 to 1/40000 of live births. It is caused by a mutat...

Background: Congenital Hypopituitarism (CH) is a rare heterogeneous genetic disorder characterized by the deficiency of pituitary hormones. CH can be associated with extra pituitary phenotypes such as midline craniofacial malformations. To date, a minority of patients carry pathogenic variants in more than 30 genes, and thus more than 80% of cases remain unresolved.Objective: To identify de novo pathogenic variants in no...

Background: Methylmalonic acidemia (MMA) is an inborn error of metabolism affecting the catabolism of essential amino acids: valine, isoleucine, methionine, and threonine. A great problem in these children is that of a growth abnormality with progressive slowing of the statural growth rate, in contrast with a normal or even accelerated weight gain. These abnormalities are accompanied by bone demineralization and muscle hypotonia.Objective and hypotheses:...

Background: Human placenta exhibits a specific miRNA expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders like preeclampsia and intrauterine growth restriction (IUGR), and are potential biomarkers for these pathologies. No studies have been performed in maternal obesity.Objective and hypotheses: (1) Define the placental miRNA profile in pregnant women with: a) pre-pregnancy (preOB) or gestational obesity (gestOB), b) gestation...

Background: In X-linked hypophosphatemia (XLH), abnormally elevated serum fibroblast growth factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption (TmP/GFR), low serum phosphorus (Pi), inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) and development of rachitic deformities.Methods: Up to four s.c. KRN23 doses were given every 28 days to 28 adults with XLH according to a dose-escalation algorithm (0.05&#1...

Background: In X-linked Hypophosphatemia (XLH), abnormally elevated serum Fibroblast Growth Factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption (TmP/GFR), low serum phosphorus (Pi), inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) and development of rachitic deformities.Methods: Up to four SC KRN23 doses were given every 28 days to 28 adults with XLH (26 completed) according to a dose-escalation algorithm (0.05&...

Objectives: In X-linked hypophosphatemia (XLH), abnormally elevated serum Fibroblast growth Factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption, low serum phosphorus, inappropriately normal 1,25-dihydroxyvitamin D, and development of rachitic deformities. The effect of KRN23 on health-related quality of life (HRQL) was assessed.Methods: Open-label KRN23 was given s.c. every 28 days up to four doses to 28 adults with XLH (2...

Background: The MAMLD1 gene (Xp28) is thought to cause disorder of sex development (DSD) in 46, XY patients, mostly presenting with hypospadias, and, recently, also gonadal dysgenesis. However, there is some controversy about the role of MAMLD1 in sex development because i) some MAMLD1 variants are also detected in normal individuals, ii) others are not present in all affected DSD individuals of the same family; iii) several MAMLD1 mutations...