Neonatal cardiac hypertrophy: the role of hyperinsulinism-a review of literature.

Hypertrophic cardiomyopathy (HCM) in neonates is a rare and heterogeneous disorder which is characterized by hypertrophy of heart with histological and functional disruption of the myocardial structure/composition. The prognosis of HCM depends on the underlying diagnosis. In this review, we emphasize the importance to consider hyperinsulinism in the differential diagnosis of HCM, as hyperinsulinism is widely associated with cardiac hypertrophy (CH) which cannot be distinguished from HCM on echocardiographic examination.

Hypertrophic cardiomyopathy in Donohue syndrome.

We report the case of a patient with Donohue syndrome who died of heart failure due to obstructive hypertrophic cardiomyopathy. A literature survey revealed that hypertrophic cardiomyopathy was present in 30% of these patients and was often fatal. Therefore, every patient with Donohue syndrome should be screened for hypertrophic cardiomyopathy.

Splice site mutations in GH1 detected in previously (Genetically) undiagnosed families with congenital isolated growth hormone deficiency type II.

Background: Congenital isolated growth hormone deficiency (IGHD) is a rare endocrine disorder that presents with severe proportionate growth failure. Dominant (type II) IGHD is usually caused by heterozygous mutations of GH1. The presentation of newly affected family members in 3 families with dominant IGHD in whom previous genetic testing had not demonstrated a GH1 mutation or had not been performed, prompted us to identify the underlying genetic cause.

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction.

Background: Congenital generalized lipodystrophy (CGL) results from mutations in AGPAT2, encoding 1-acyl-glycerol-3-phosphate-acyltransferase 2 (CGL1; MIM 608594), BSCL2, encoding seipin (CGL2; MIM 269700), CAV1, encoding caveolin1 (CGL3; MIM 612526) or PTRF, encoding polymerase I and transcript release factor (CGL4; MIM 613327). This study aims to investigate the genotype/phenotype relationship and search for a possible pathogenic mechanism in a patient with CGL.

Design: Case report.

Recognition of heat shock protein 60 epitopes in children with type 1 diabetes.

Background: Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA-DR-binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission.

Methods: Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis.

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.

Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type 1 diabetes with near-optimal glycaemic control during pregnancy.

Background: High maternal glucose concentrations during diabetic pregnancy may lead to health problems in the offspring later in life. We showed in a previous nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy care was good and a near-optimal glycaemic control during pregnancy was achieved (mean HbA1c 6.2%).

Bone mineral density in children with moderate to severe atopic dermatitis.

Background: Low bone mineral density (BMD) has been reported in 30.4% of adult patients with atopic dermatitis (AD).

Objective: The aim of this study was to determine the prevalence of low BMD in children with moderate to severe AD and to investigate the relation between BMD and corticosteroid and cyclosporine therapy.

Characterization of a novel loss-of-function mutation of PAX8 associated with congenital hypothyroidism.

Background: Congenital hypothyroidism (CH) is a common endocrine disease that occurs in about 1:3000 newborns. In 80-85% of the cases, CH is presumably secondary to thyroid dysgenesis (TD), a defect in the organogenesis of the gland leading to an ectopic (30-45%), absent (agenesis, 35-40%) or hypoplastic (5%) thyroid gland. The pathogenesis of TD is still largely unknown.

[Antipsychotics and metabolic abnormalities in children and adolescents: a review of the literature and some recommendations].

Background: Adult patients with schizophrenia and bipolar disorder have an increased risk of developing the metabolic syndrome. This is due to their psychiatric illness and to the use of antipsychotic drugs. Children and adolescents are being treated more and more with antipsychotics.

Risk factors for childhood overweight in offspring of type 1 diabetic women with adequate glycemic control during pregnancy: Nationwide follow-up study in the Netherlands.

Objective: Pregnancy in type 1 diabetic women remains a high-risk situation for both mother and child. In this study, we investigated long-term effects on body composition, prevalence of overweight, and insulin resistance in children of type 1 diabetic women who had had adequate glycemic control during pregnancy (mean A1C 6.2%), and we related their outcome to perinatal factors, including macrosomia (birth weight >90th percentile).

[Follow-up of adult women with Turner's syndrome in a cohort study in Utrecht].

Objective: To evaluate the follow-up of adult women with Turner's syndrome.

Design: Cross-sectional study using questionnaires.

Method: In August 2005 questionnaires were sent to 5 adult women with Turner's syndrome who were known to the Wilhelmina Children's Hospital in Utrecht, The Netherlands.

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf-Hirschhorn syndrome.

The Wolf-Hirschhorn syndrome (WHS (MIM 194190)), which is characterized by growth delay, mental retardation, epilepsy, facial dysmorphisms, and midline fusion defects, shows extensive phenotypic variability. Several of the proposed mutational and epigenetic mechanisms in this and other chromosomal deletion syndromes fail to explain the observed phenotypic variability. To explain the complex phenotype of a patient with WHS and features reminiscent of Wolfram syndrome (WFS (MIM 222300)), we performed extensive clinical evaluation and classical and molecular cytogenetic (GTG banding, FISH and array-CGH) and WFS1 gene mutation analyses.

An amino-terminal DAX1 (NROB1) missense mutation associated with isolated mineralocorticoid deficiency.

Context: Mutations in DAX1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene 1; NR0B1) cause X-linked adrenal hypoplasia congenita, a disease characterized by primary adrenal failure, testicular dysgenesis, and gonadotropin deficiency. Most DAX1 mutations are deletions, nonsense, or frameshift mutations that markedly impair its transcriptional activity. Missense mutations have been restricted to the carboxy-terminal domain and are associated with more variable clinical phenotypes.

[From gene to disease; congenital adrenal hypoplasia and the DAX-1 gene].

Congenital adrenal hypoplasia is an X-linked disorder resulting in adrenocortical deficiency, failure to complete puberty due to hypogonadotrophic hypogonadism, and infertility. The disease is caused by mutations in the DAX-1 gene. The DAX-1 protein is a transcription inhibitor; it represses the transcription of other, as yet mostly unknown, genes.

[When is a tall child too tall?].

3 children presented with tall stature. A 14-year-old girl of 179.6 cm was found to be within her target height range and was treated with oestrogen.

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.

Laparoscopic diagnosis and cure of hyperinsulinism in two cases of focal adenomatous hyperplasia in infancy.

Persistent hyperinsulinemic hypoglycemia of infancy or congenital hyperinsulinism of the neonate is a rare condition that may cause severe neurologic damage if the disease is unrecognized or inadequately treated. Current treatment aims to restore normal blood glucose levels by providing a carbohydrate-enriched diet and drugs that inhibit insulin secretion. If medical treatment fails, then surgery is required.

Laparoscopic identification and removal of focal lesions in persistent hyperinsulinemic hypoglycemia of infancy.

Background: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a heterogeneous condition. A number of children have focal lesions, and removal of these lesions is curative. However, these lesions are difficult to detect, even during surgery.

Human and mouse TPIT gene mutations cause early onset pituitary ACTH deficiency.

Tpit is a highly cell-restricted transcription factor that is required for expression of the pro-opiomelanocortin (POMC) gene and for terminal differentiation of the pituitary corticotroph lineage. Its exclusive expression in pituitary POMC-expressing cells has suggested that its mutation may cause isolated deficiency of pituitary adrenocorticotropin (ACTH). We now show that Tpit-deficient mice constitute a model of isolated ACTH deficiency (IAD) that is very similar to human IAD patients carrying TPIT gene mutations.

Lung function abnormalities in children with type I diabetes.

Recent developments in intrabronchial administration of insulin raise lung function in patients with type I diabetes as important issue. Several studies in adults report abnormalities of lung function of these patients. The aim of this study was to investigate lung function in children with type I diabetes.

Genotype versus phenotype in families with androgen insensitivity syndrome.

Androgen insensitivity syndrome encompasses a wide range of phenotypes, which are caused by numerous different mutations in the AR gene. Detailed information on the genotype/phenotype relationship in androgen insensitivity syndrome is important for sex assignment, treatment of androgen insensitivity syndrome patients, genetic counseling of their families, and insight into the functional domains of the AR. The commonly accepted concept of dependence on fetal androgens of the development of Wolffian ducts was studied in complete androgen insensitivity syndrome (CAIS) patients.