Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years.

Methods: This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA.

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study.

Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control.

Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing.

Results: A total of 363 children were enrolled (28 centers, 8 countries).

Severity estimation of very-long-chain acyl-CoA dehydrogenase deficiency via C-fatty acid loading test.

Background: The clinical severity of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is difficult to predict using conventional diagnostic methods.

Methods: Peripheral blood mononuclear cells obtained from 14 VLCAD deficiency patients and 23 healthy adults were loaded with carbon-13-universally labeled (U-C-) fatty acids. Differences in acylcarnitine ratios between the patients and healthy groups and correlations between acylcarnitine ratios and a newly established clinical severity score (CSS) in the patient group were statistically examined.

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.

Purpose: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via mutation detection.

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous mutations. To date, 13 patients affected by mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age.

Congenital craniopharyngioma treated by radical surgery: case report and review of the literature.

Purpose: Craniopharyngiomas are 5-10 % of all pediatric tumors, but are seldomly encountered in the perinatal period. Only seven instances of a truly antenatal diagnosis of a congenital craniopharyngioma that subsequently underwent radical surgery have been reported. We present the case of a patient who received the diagnosis of a suprasellar tumor during the prenatal period and received radical surgery.

Detection of glucokinase gene defects in non-obese Japanese children diagnosed with diabetes by school medical examinations.

We examined children who were diagnosed with asymptomatic type 2 diabetes by school medical examinations to investigate the existence of glucokinase (GCK) gene defects in this group. Among 20 children diagnosed with asymptomatic type 2 diabetes by school medical examinations between 2003 and 2009 at our 2 hospitals, 8 were classified as non-obese type. Among them, we screened 5 children (2 boys and 3 girls; age: 8-13 years) who had mild elevation of fasting plasma glucose (108-134 mg/dL) with slightly high internationally standardized HbA1c levels (6.

Increased urinary angiotensinogen is precedent to increased urinary albumin in patients with type 1 diabetes.

Background: We previously reported that kidney and urinary angiotensinogen levels were significantly increased before the development of diabetic nephropathy in diabetic rats. To address this system in humans, we have developed an enzyme-linked immunosorbent assay for human angiotensinogen and reported that urinary excretion of angiotensinogen levels is enhanced in patients with chronic kidney disease, including patients with type 2 diabetes. On the basis of these findings, this study was performed to demonstrate that urinary angiotensinogen levels increased before the onset of microalbuminuria and that urinary angiotensinogen can be an early biomarker of intrarenal renin-angiotensin system status in normoalbuminuric patients with type 1 diabetes compared with age- and sex-matched control subjects.

Relatively small birth size and accelerated early growth of Japanese type 1 diabetic children with younger onset.

We investigated the changes of anthropometrical parameters in Japanese children with type 1 diabetes (T1DM) from birth to the onset of diabetes. One-hundred ninety-nine children (79 males and 120 females) diagnosed between 0-16 yr of age during the period between 1990 and 2003 were the subjects of this study. The subjects were categorized into 3 groups according to onset age (0-5 yr; n=74, 5-10 yr; n=61, 10-16 yr; n=64).

Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation.

The octanoylation of Ser3 is essential for the biological function of ghrelin. We examined the concentrations of the n-octanoylated active-form ghrelin in cord and neonatal blood using an RIA system that specifically recognized n-octanoylated ghrelin, as well as a system that measured the total ghrelin concentration. Plasma levels of active ghrelin in cord blood ranged from 7.

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight.

Objective: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones.

Design: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.

Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance.

To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8).