A New Tool to Identify Pediatric Patients with Atypical Diabetes Associated with Gene Polymorphisms.

Backgruound: Recent diabetes subclassifications have improved the differentiation between patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus despite several overlapping features, yet without considering genetic forms of diabetes. We sought to facilitate the identification of monogenic diabetes by creating a new tool that we validated in a pediatric maturity-onset diabetes of the young (MODY) cohort.

Methods: We first created the DIAgnose MOnogenic DIAbetes (DIAMODIA) criteria based on the pre-existing, but incomplete, MODY calculator.

IGF1 haploinsufficiency in children with short stature: a case series.

Context: Short stature in children is a common reason for referral to pediatric endocrinologists. The underlying cause of short stature remains unclear in many cases and patients often receive unsatisfactory, descriptive diagnoses. While textbooks underline the rarity of genetic causes of growth hormone (GH) insensitivity and the severity of its associated growth failure, increased genetic testing in patients with short stature of unclear origin has revealed gene defects in the GH/insulin-like growth factor (IGF-I) axis associated with milder phenotypes.

Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study.

Background: Recombinant human growth hormone has been used for more than 30 years and its indications have increased worldwide. There is concern that this treatment might increase mortality, but published data are scarce. We present data from the entire dataset of all eight countries of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium, with the aim of studying long-term overall and cause-specific mortality in young adult patients treated with recombinant human growth hormone during childhood and relating this to the underlying diagnosis.

DNA Methylation Profiling and Genomic Analysis in 20 Children with Short Stature Who Were Born Small for Gestational Age.

Purpose: In a significant proportion of children born small for gestational age (SGA) with failure of catch-up growth, the etiology of short stature remains unclear after routine diagnostic workup. We wanted to investigate if extensive analysis of the (epi)genome can unravel the cause of growth failure in a significant portion of these children.

Patients And Methods: Twenty SGA children treated with GH because of short stature were selected from the BELGROW database of the Belgian Society for Pediatric Endocrinology and Diabetology for exome sequencing, single-nucleotide polymorphism (SNP) array and genome-wide methylation analysis to identify the (epi)genetic cause.

Risk of Meningioma in European Patients Treated With Growth Hormone in Childhood: Results From the SAGhE Cohort.

Context: There has been concern that GH treatment of children might increase meningioma risk. Results of published studies have been inconsistent and limited.

Objective: To examine meningioma risks in relation to GH treatment.

Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study.

Context: Growth hormone (GH) is prescribed for an increasing range of indications, but there has been concern that it might raise cancer risk. Published data are limited.

Objective: To examine cancer risks in relation to GH treatment.

High unacylated ghrelin levels support the concept of anorexia in infants with prader-willi syndrome.

Background: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is found in both acylated (AG) and unacylated (UAG) forms in the circulation.

Expanding the CHARGE Geno-Phenotype: A Girl with Novel CHD7 Deletion, Hypogonadotropic Hypogonadism, and Agenesis of Uterus and Ovaries.

Background: CHARGE syndrome is a variable entity. Clinical diagnosis is based on the Blake-Verloes criteria and can be confirmed by identifying a mutation or deletion in the CHD7 gene. Hypoplasia of the male genitalia and lack or incomplete secondary sexual development in both sexes is a common feature, and is most often attributable to hypogonadotropic hypogonadism which is described in >80% of the CHARGE patients.

Central precocious puberty caused by mutations in the imprinted gene MKRN3.

Background: The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Early activation of the hypothalamic-pituitary-gonadal axis results in central precocious puberty. The timing of pubertal development is driven in part by genetic factors, but only a few, rare molecular defects associated with central precocious puberty have been identified.

Insulin sensitivity modulates the growth response during the first year of high-dose growth hormone treatment in short prepubertal children born small for gestational age.

Aim: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH).

Methods: Randomized, open-label, 24-month intervention study in 40 short prepubertal SGA children [age (mean ± SD) 5.3 ± 1.

Intrathoracic lymphadenitis caused by Mycobacterium avium and Mycobacterium tuberculosis in an immunocompetent child.

By means of a DNA probe assay (INNO-LiPA) we identified 2 different mycobacterial strains (Mycobacterium avium and Mycobacterium tuberculosis complex) from a mediastinal lymph node biopsy obtained from an apparently immunocompetent 7.5-year-old girl, whereas culture grew only M. avium.

Growth hormone treatment and fat redistribution in children born small for gestational age.

Objective: To determine whether in children born small for gestational age (SGA) high-dose growth hormone (GH) treatment is not only associated with catch-up of growth and with gain of lean mass, but also with a more central fat distribution.

Study Design: Short children who were SGA (n = 25; age [mean +/- SD], 5.3 +/- 1.

Neonatal cholestatic jaundice as the first symptom of a mutation in the hepatocyte nuclear factor-1beta gene (HNF-1beta).

This report describes the phenotype of a novel de novo heterozygous frameshift mutation in the hepatocyte nuclear factor-1beta gene (HNF-1beta or TCF2) manifest as a neonatal paucity of intrahepatic bile ducts. HNF-1beta mutations should be considered in neonates with cholestatic jaundice associated with renal malformation or diabetes mellitus.

Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations.

Tpit is a T box transcription factor important for terminal differentiation of pituitary proopiomelanocortin-expressing cells. We demonstrated that human and mouse mutations of the TPIT gene cause a neonatal-onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid replacement, IAD can lead to neonatal death by acute adrenal insufficiency.

Rhabdomyolysis in diabetic ketoacidosis.

Rhabdomyolysis is a potentially lethal disorder, characterized by elevated serum concentrations of creatine kinase (CK) due to skeletal muscle injury. In this paper a patient with diabetic ketoacidosis (DKA) is reported who developed rhabdomyolysis (maximum CK level, 37,700 U/L; normal, < 170 U/L), anemia (6.2 g/dL) and thrombocytopenia (16,000/microL).