Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy.

Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms' tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.

The Synergistic Effects of a Complementary Physiotherapeutic Scheme in the Psychological and Nutritional Treatment in a Teenage Girl with Type 1 Diabetes Mellitus, Anxiety Disorder and Anorexia Nervosa.

Type 1 diabetes mellitus (T1DM) is a chronic disease that can affect the physical and mental health of children and adolescents, often leading to anxiety disorders with chronic activation of the hypothalamic axis (HPA). Moreover, a great proportion of adolescents with T1DM also demonstrate anorexia nervosa (AN), due to the increased preoccupation with food and the need to have an acceptable body image. Herein is described the first case study of an adolescent patient diagnosed with T1DM, anxiety disorder (AD), and AN. A 14-year-old girl with T1DM since the age of 12 years presented weight loss at age 13 years and 3 months and low body mass index (BMI), which did not improve despite dietary recommendations and adequate disease control. Additionally, she presented menstrual disorders at the age of 12 years and 11 months (menstrual age 12 years and 1 month). A psychological evaluation of the teenager was conducted using a semi-structured interview that assessed perceived stress, health status, quality of life, and depression. AD and AN were diagnosed and the patient initiated an intervention focusing on psychological health and nutrition and which incorporated physiotherapeutic relaxation sessions and breathing exercises. After 3 months of treatment, the patient's BMI was increased, and a normal menstrual cycle was apparent. These results have since remained consistent. Stress leads to the appearance of AN and menstrual disorders. Therefore, physiotherapeutic programs could reduce stress and effectively ameliorate AN and AD.

Late diagnosis of 3ß-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene.

OBJECTIVES: 3ß-Hydroxysteroid dehydrogenase (3ß-HSD) deficiency is a rare type of congenital adrenal hyperplasia caused by recessive loss-of-function mutations in HSD3B2 gene. CASE PRESENTATION: We report an 8.5-year-old, 46XY, Roma boy with advanced adrenarche signs born to consanguineous parents. He was born at term with ambiguous genitalia. At 15 days of age, he underwent replacement therapy with hydrocortisone and fludrocortisone due to a salt wasting (SW) crisis and adrenal insufficiency. At 3.5 years, he was admitted again with SW crisis attributed to the low - unadjusted to body surface area - hydrocortisone dose and presented with bilateral gynecomastia and adrenarche. At 8.5 years, his bone age was four years more advanced than his chronological age and he was prepubertal, with very high testosterone levels. Gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis revealed the typical steroid metabolic fingerprint of 3ß-HSD deficiency. Sequencing of the HSD3B2 gene identified in homozygosity the novel p.Lys36Ter nonsense mutation. Furthermore, this patient was found to be heterozygous for p.Val281Leu in the CYP21A2 gene. Both parents were identified as carriers of the p.Lys36Ter in HSD3B2. CONCLUSIONS: A novel nonsense p.Lys36Ter mutation in HSD3B2 was identified in a male patient with hypospadias. 3ß-HSD deficiency due to mutations in the HSD3B2 gene is extremely rare and the finding of a patient with this rare type of disorders of sex development (DSD) is one of the very few reported to date. The complexity of such diseases requires a multidisciplinary team approach regarding the diagnosis and follow-up.

The Beneficial Effect of the Mobile Application Euglyca in Children and Adolescents with Type 1 Diabetes Mellitus: A Randomized Controlled Trial.

Background: Euglyca® is a mobile application which we developed for children and adolescents suffering type 1 diabetes mellitus (T1DM) for calculation of the appropriate insulin bolus dose by importing in the equation carbohydrates, lipids, glucose levels, and personalized parameters. Aim of this study is to evaluate the efficacy of this application on patients' glycemic control and satisfaction. Subjects and Methods: Eighty children and adolescents (aged 13.5 ± 2.8 years old, mean ± standard deviation) with T1DM were included in the study and were randomly and equally assigned in two groups. Patients were asked to use Euglyca for the calculation of the bolus insulin dose in the E group and to pursue their routine calculations in the C group (controls). At baseline and at 3, 6, and 12 months following the initial visit, glycated hemoglobin (HbA1c) values, percentages of hypoglycemias, hyperglycemias, and normoglycemias were determined for each patient, while Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to assess patients' treatment satisfaction at baseline and at 6 and 12 months. Results: Children and adolescents in the E group had a statistically significant decrease in HbA1c values and increase in percentages of normoglycemias and DTSQ scores, in comparison to children and adolescents in the C group. In the E group, a statistically significant positive linear correlation was found between DTSQ score and percentages of normoglycemias and a statistically significant negative correlation between changes in percentages of normoglycemias (Δnormoglycemias) and changes in HbA1c (ΔHbA1c). Conclusions: The use of the mobile application Euglyca contributes to the improvement of glycemic control and treatment satisfaction of children and adolescents with T1DM.

High-sensitivity C-reactive protein levels and metabolic disorders in obese and overweight children and adolescents.

OBJECTIVE: To compare high-sensitivity C-reactive protein (hsCRP) levels in obese and overweight children and adolescents to normal-weight individuals as well as to compare hsCRP levels in overweight children/adolescents with and without additional metabolic disorders such as metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), and prediabetes. METHODS: 54 consecutive obese children and adolescents with a body mass index (BMI) ≥ 95th centile and 50 overweight children and adolescents with BMI values between 85th and 95th centiles were screened for MS, prediabetes and NAFLD. Serum hsCRP levels were measured in all the participants and in 40 age-matched normal-weight individuals (controls). RESULTS: HsCRP levels were significantly increased in obese and overweight subjects as compared to the control group, (0.61 ± 1.08 vs. 0.05 ± 0.18 mg/dL,p<0.001 and 0.33 ± 0.25 vs. 0.05 ± 0.18 mg/dL, p<0.001, respectively). HsCRP levels were similar between obese and overweight subjects (p=0.109). Obese and overweight children with NAFLD had significantly higher levels of hsCRP compared to their counterparts without NAFLD (0.78 ± 1.4 vs. 0.34 ± 0.31 mg/dL, p=0.016). The levels of hsCRP were comparable in the obese and overweight children/adolescents with and without MS and with or without prediabetes(0.95 ± 1.66 vs. 0.35 ± 0.27 mg/dL, p = 0.096 and 0.43 ± 0.34 vs. 0.53 ± 1.0mg/dL, p=0.589, respectively). CONCLUSIONS: HsCRP is significantly elevated in children and adolescents with excess weight as compared to normal-weight individuals. In addition,children and adolescents with excessive weight and NAFLD show increased levels of hsCRP compared to their counterparts with normal liver.

A Bayesian approach to copy-number-polymorphism analysis in nuclear pedigrees.

Segmental copy-number polymorphisms (CNPs) represent a significant component of human genetic variation and are likely to contribute to disease susceptibility. These potentially multiallelic and highly polymorphic systems present new challenges to family-based genetic-analysis tools that commonly assume codominant markers and allow for no genotyping error. The copy-number quantitation (CNP phenotype) represents the total number of segmental copies present in an individual and provides a means to infer, rather than to observe, the underlying allele segregation. We present an integrated approach to meet these challenges, in the form of a graphical model in which we infer the underlying CNP phenotype from the (single or replicate) quantitative measure within the analysis while assuming an allele-based system segregating through the pedigree. This approach can be readily applied to the study of any form of genetic measure, and the construction permits extension to a wide variety of hypothesis tests. We have implemented the basic model for use with nuclear families, and we illustrate its application through an analysis of the CNP located in gene CCL3L1 in 201 families with asthma.

A boy with McCune-Albright syndrome associated with GH secreting pituitary microadenoma. Clinical findings and response to treatment.

The McCune-Albright Syndrome (MAS) is a sporadic rare disease first described in 1936 by McCune and separately by Albright. MAS is characterized by a triad of physical signs: café-au-lait spots, polyostotic fibrous dysplasia and autonomous endocrine hyperfunction. MAS is predominantly observed in girls and is rarely reported in males. We report the case of a 9-year old boy with gonadotropin independent precocious puberty, café-au-lait spots, polyostotic fibrous dysplasia and growth hormone hypersecretion.