Volume 24, Issue 5-6

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Objective: To compare the characteristics of a set of weight-related and well-being variables among adolescents according to gender and age. It was hypothesised that time of puberty, not age in itself, might be the turning point for gender dissimilarities. Methods: Data were drawn from the Portuguese 2006 HBSC/WHO database and were disaggregated by gender and age group. Groups were compared for dieting, body image, health perception and happiness variables on the bivariate level using cross-tabulations. Separate analysis of the dependent variables was further conducted for 11-year-olds comparing males with pre- and post-menarche females. Results: Dieting and a negative body image were consistently more prevalent among girls and increased with age. At 11 years significantly more post-menarche girls were dieting and dissatisfied with their body image than boys and their pre-menarche counterparts. A poor self-rated health and the perception of unhappiness tended to be more common among older adolescents and among girls. Conclusions: Pubertal timing, and not age in itself, appears as the turning point for gender dissimilarities. Both gender- and age-specific differences as well as pubertal timing have to be taken into account by any physician when assessing an adolescent in order to be able to adapt the intervention.

Objective: The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves’ disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI). Design, setting and participants: Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (≥0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (≥7.5 mg/kg, n=45). Main outcome measures: The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared. Results: Mean durations for normalization of T4 (±SD) were 1.7±1.0 months in group M and 2.3±2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1±3.3) was significantly longer than those in the other subgroups (M1: 1.9±1.2; M2: 1.4±0.7; P2; 1.7±1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40). Conclusions: PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Objectives: 1) To evaluate the effects of glucocorticoid (GC) doses on bone mineral density (BMD) in children with congenital adrenal hyperplasia (CAH), 2) Investigate other factors influencing BMD. Methods: Twenty-six children with CAH and 11 healthy controls included in the study. All of the patients were examined with dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000/W densitometer. The metabolic control state, age at diagnosis GC dose (mg/m 2 /day), pubertal status, 17 hydroxyprogesterone (17 OHP) levels, bone age (BA), and lumber BMD were evaluated in all cases. BMD (g/cm 2 ), BMD z-score corrected to National Standards (cNS-BMD z-score), BMD z-score corrected to BA (cBABMD), bone mineral content (BMC), BMC corrected to puberty (cPBMC), and bone area (BAR) values were determined. Patients were grouped according to mean on-therapy serum 17 OHP levels as tight control (17 OHP<10 nmol/L) (n:13) and poor control (17 OHP>10 nmol/L) (n:13). All groups were compared with each other. Results: The age range was 2.1–15.7 years and the mean age (±SD) 9.3 (±3.5) years. There were no significant differences between the groups in terms of GC doses, lumbar BMD values [BMD (g/cm 2 ), BMD z-score corrected to National Standards (cNS-BMD z-score), BMD z-score corrected to BA (cBABMD), bone mineral content (BMC), BMC corrected to puberty (cPBMC), and bone area (BAR)]. However, the BMI value was higher in children with CAH than normal healthy controls. The BA of the poor control, late diagnosed groups and male patients were higher than tight control, early diagnosed group and female patients, respectively. BMC and BA were lower than the control group in tight control with early diagnosed patients. The cBABMD z-score was lower in males with poor control than males with tight control. There were no similar results in female patients. Conclusions: Although GC treatment seems not to influence BMD in CAH patients in our study, further studies are needed to additionally evaluate daily calcium (Ca) intake, polymorphism of vitamin D receptor, ethnic factors (strict Islamic dress, etc.), socioeconomic status, and 24-h urinary free cortisol level.

Bisphosphonate treatment for bone fragility has expanded beyond children with osteogenesis imperfecta (OI) to those with other causes of low bone mass. However, clinical efficacy and optimal dosing in non-OI patients has not been established. We conducted a retrospective descriptive study of patients with non-OI-related bone fragility to describe the effects of two different pamidronate treatment regimens on the bone mineral density (BMD) and fracture rate of these children. Between 2000 and 2009, 15 non-OI patients aged 8–16 years received pamidronate 1 mg/kg intravenously for 1 day every 3 months (4 mg/kg/year) or 1 mg/kg/day for 3 days every 4 months (9 mg/kg/year). After 1 year of pamidronate, the two groups had a comparable increase in adjusted BMD and reduction in fragility fractures. No serious adverse effects were observed. Since the long-term effects of bisphosphonate are unknown, large trials are needed to delineate the minimal effective dose in these patients.

Improving the final adult height is one of the most important aims for treatment of central precocious puberty. Stanozolol (ST) is a synthetic derivative of androgen. In this study, we investigated the effects and the mechanisms of ST on the proliferation of growth plate chondrocytes isolated from adolescent rats treated with gonadotropin-releasing hormone analogue (GnRHa). Treatment with ST resulted in time- and concentration-dependent effects on proliferation as determined by MTT and proliferating cell nuclear antigen (PCNA) assays. Western blotting showed that ST increased the phosphorylation level of the estrogen receptor α (ERα), but not the androgen receptor (AR). Pharmacological inhibition of ERα and mitogen-activated protein kinase (MAPK) attenuated the effects of ST on the proliferation of growth plate chondrocytes. A molecular dynamics simulation showed hydrophobic interactions between ST and ERα. These results suggested that ERα, but not AR, partially mediates the ST-driven proliferation of growth plate chondrocytes, and that multiple pathways may be involved in the mechanism of action of ST.

Background: McCune-Albright syndrome (MAS) is a clinical syndrome with low incidence, and its concurrence with pituitary GH adenoma is rare. Little of the history, treatment and outcome has been studied. Method: Follow-up of a 37-year-old male patient of MAS associated with pituitary GH adenoma was performed continuously recording the disease development and the treatment process until death, after which an autopsy was performed. Results : Radiation therapy (RT) efficaciously controlled GH hypersecretion, however, it may have been the cause of the malignant transformation of the dysplastic bone tissue, which eventually caused brain hernia and death; autopsy demonstrated that the cranium had significant thickening (as much as 10 cm), the pathological diagnosis was fibrous dysplasia of bone associated with chondrosarcoma; and undifferentiated chondrosarcoma with malignant fibrous histocytoma subtype in the sellar region; nodular goiter with the thyroid gland, one nodus was pathologically demonstrated as papillary carcinoma. Conclusion: GH adenoma, present in a patient with MAS, might be cured by RT; but the risk of malignant transformation of the dysplastic bone tissue in the field of irradiation make it controversial. Lessons from the case reported here told us that we should take great caution when recommending RT for patients like this.

Objective: Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipo­kines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children. Methods: We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans , age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression. Results: There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05). Conclusion: Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Background: Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and hyperphosphatemia in association with an increased secretion of parathyroid hormone (PTH) due to decreased target tissue responsiveness to PTH. Patients with PHP type Ia are not only resistant to PTH, but also to other hormones that bind to receptors coupled to stimulatory G protein (Gsα). PHP Ia and Albright hereditary osteodystrophy (AHO) are caused by a reduced activity of the Gsα protein. Heterozygous inactivating Gs alpha ( GNAS ) gene mutations have been identified in these patients. Methods: We studied a boy with PHP Ia. During follow-up the patient developed elevated liver enzyme serum levels and abdominal discomfort. Gsα activity was measured in erythrocyte membranes from the patient and the GNAS coding region of Gsα sequenced. Results: Gsα activity was reduced (62%) and molecular analysis revealed a new heterozygous GNAS gene mutation (D196N). Gallstones were diagnosed and cholecystectomy was performed. Biochemical analysis revealed cholesterol stones, a condition that was not reported before in PHP Ia. Conclusions: Cholesterol gallstones may rarely be associated with PHP Ia and should be taken into account.

Background: Despite the childhood obesity epidemic, few obese children receive therapy and relatively few weight management multidisciplinary programs exist. Objective and methods : The objective of this study was to examine the patterns and causes for obese children referrals to a tertiary multidisciplinary childhood obesity treatment program. A total of 227 children (10.6±2.6 years; 108 boys, 119 girls) were evaluated at the beginning of the programs for personal and familial demographic and anthropometric details, the referring agent to the program, and the main reasons for participation and for the child’s desire to lose weight. Results: The majority of participants had an obese family member (83%), in particular an obese parent (62%). The majority of patients were self-referred (86.8%), mainly by their mothers (74%). Only a small fraction were referred by healthcare providers (15.4%). The desire to improve appearance (44.5%), social/psychological issues (39.2%) and the will to improve fitness (29.5%) were the main reasons for joining the program. Conclusion : Understanding the motives for participation and referral patterns can improve recruitment and participation of obese children in weight reduction intervention programs.

Background: Turner syndrome (TS) patients present low bone mineral density (BMD) and increased fracture risk, probably due to a genetic defect aggravated by hormonal deficiency. Aim: To study the relationship between vitamin D receptor (VDR) gene polymorphisms and BMD and bone parameters in TS patients. Methods: DNA from 65 TS patients and 110 controls was amplified by PCR and digested with Fok I, Bsm I and Apa I restrictases. Lumbar and femoral BMD were determined by DEXA and serum intact parathyroid hormone, osteocalcin and β-CrossLaps by electrochemiluminescence. Results: Genotype distribution within the Apa I site was different in both groups: genotype Aa was more abundant in TS (63.8% vs. 41.3%; p<0.01), whereas AA predominated in controls (33.9% vs. 15.5%; p<0.01). Patients carrying genotype bb ( Bsm I) or ff ( Fok I) had lower BMD than those with other genotypes (p<0.01 and p<0.05, respectively). Conclusion : Bsm I and Fok I polymorphic sites of VDR could be genetic determinants of BMD in TS patients.

Background : Alterations in plasma leptin and adiponectin concentrations are associated with an adverse metabolic profile in obese children. Objective : To simultaneously assess multiple factors with possible effects on plasma leptin and adiponectin concentrations in healthy, non-obese children. Subjects : We studied 170 healthy non-obese children (86 males, age 10±1.5 years), with available medical records from birth. Methods : Plasma leptin and adiponectin concentrations were assessed by immunoassay. The ratio of current weight/birth weight (WBWR) was used as an index of children growth from birth. Children’s intensity of physical activity and parental characteristics were also assessed. Results : Leptin was positively associated with WBWR (p<0.0001); parental smoking (analysis of variance, ANOVA; p=0.03) and parental obesity (ANOVA; p<0.001) were negatively associated with breastfeeding (p<0.01) and children’s access to exercise (p<0.0001). Adiponectin was negatively associated with WBWR (p<0.0001) and parental smoking (p=0.04), with an additive negative effect of parental smoking status and parental obesity on children’s adiponectin levels (ANOVA; p=0.02). Conclusions : Children’s and parental factors are related and could possibly influence leptin and adiponectin concentrations in healthy non-obese children. Early preventive strategies that target both children and parents could improve the profile of adipocytokine in these children.

Objective : As the prognosis for final height is unfavorable for children with idiopathic short stature (ISS), we studied the pubertal growth dynamics in these children, which is a determinant factor in final height. Subjects/methods : In a retrospective cohort study, we analyzed the pubertal period, age of puberty and peripubertal growth in 50 children with ISS. Results : The onset of puberty occurred later. Growth rate tended to become increasingly subnormal in the prepubertal period and height was –2.45 SD at puberty onset. Growth reaccelerated at this point, which tended to correct the deviation from the mean height, but it was insufficient to obtain a normal final height. Conclusions : The dynamics of growth in children with ISS showed a distinct pattern in the prepubertal and pubertal periods and puberty is significantly delayed in this population. These patterns could explain the unfavorable prognosis for children with ISS.

Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children’s Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly.

Purpose : To investigate CYP17A1 gene mutations in Chinese patients with 17α-hydroxylase deficiency. Methods : Clinical data were retrospectively analyzed. CYP17A1 mutations were detected in two cases with 17α-hydroxylase deficiency. Genomic DNA was isolated from blood samples and eight primers pairs were used to amplify eight exons and exon–intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel electrophoresis and then directly sequenced. Sequencing results were compared to the established human CYP17A1 sequence. Results : Two compound mutations were identified: TAC→AA at codons 436–438 on exon 6, causing the amino acid missense mutation Y329K/418X; and deletion of the 9-bp sequence GACTCTTTC at codons 487–489 on exon 8, causing deletion of three amino acids (Asp-Ser-Phe). Conclusion : D487_F489del and Y329K, 418X CYP17A1 mutations were identified in our two patients. A literature review revealed that the main CYP17A1 mutations in the Chinese population are missense and splicing defects, and exons 8 and 6 are most frequently involved.

Background: The median age at thelarche in Thai girls has decreased from 10.3 to 9.4 years over the last 20 years. An age at thelarche of 7.0–9.0 years, which is earlier than in the general population, is considered as early puberty. Objective: To study the pattern of pubertal development in Thai girls with early puberty. Study design: A total of 104 girls with breast development at 7.0–9.0 years who attended Songklanagarind Hospital between 2003 and 2005 were followed up until they attained their near-final height (NFH). Results: The mean age at initial evaluation was 8.5±1.0 years. The average age at menarche and on attaining NFH was 10.2±0.9 and 12.6±0.4 years, respectively. The average NFH was 154.0±4.9 cm, which was similar to the target height of 153.1±4.8 cm. Comparison of girls who were normal weight and obese (weight-for-height >120%) revealed that the latter had an earlier age at menarche (9.8±0.8 vs. 10.5±0.8 years, p<0.01) and reached their NFH at a younger age (12.2±0.4 vs. 12.9±0.4 years, p=0.02). However, normal-weight and obese girls reached approximately the same NFH (155.8±4.8 vs. 153.1±4.0 cm, p=0.058). Conclusion: Girls with early puberty attained NFH similar to their genetic potential. Obese girls attained NFH at an earlier age and had the same NFH as normal-weight girls.

Background: Some children with congenital hypothyroidism (CH), have persistent hyperthyrotropinemia despite good compliance with levothyroxine. Objective : To evaluate combination therapy of liothyronine (cytomel ® ) with levothyroxine in CH with persistent hyperthyrotropinemia. Patients and methods : Files were reviewed retrospectively. Eight female patients with persistently high levels of TSH and upper normal FT4 levels were given either 6.25 or 12 μg liothyronine and the levothyroxine dose was reduced appropriately. Pre- and post-intervention hormone levels and drug doses were evaluated. Results : TSH decreased in 8/8 and normalized in 6/8 patients. FT4 and free tri-iodothyronine (FT3) remained normal. The levothyroxine-equivalent dose on the combination was 5.0±0.3 μg/kg/day in infants and 3.4±0.4 μg/kg/day in children above 2.5 years. Infants required higher liothyronine doses compared with older children (0.66±0.01 vs. 0.3±0.05 μg/kg/day). Conclusions : Combined therapy can achieve normal TSH levels with normal FT4 and FT3. Further long-term research is required to investigate effects on neurodevelopmental outcome.

A total of 20 children with benign transient hyperphosphatasemia were prospectively evaluated with no additional investigations recommended except repeat serologic evaluation in 2–3 months. The average age of our patients was 2.5 years (range 1 year 2 months–5 years 10 months). The serum levels of alkaline phosphatase averaged 2383 IU/L (range 1013–5700 IU/L). Levels returned to normal within several months. This condition should be recognized by the clinician in order not to put patients through lengthy, expensive and unnecessary investigations.

Objective: The associations between peak bone mineral density (BMD) and body composition with 25 hydroxyvitamin D (25OHD) levels in healthy young adults were evaluated. Methods: The number of participants was 464; 347 women and 117 men. The mean age was 24.3 years (range 17–31 years). BMD of the lumbar spine, total body and femoral neck (FN) and body composition were measured by dual energy X-ray absorptiometry. Volumetric BMD, bone mineral apparent density (BMAD), of the lumbar spine and FN was calculated. Results: In females, 25OHD level was positively associated with FN BMD and BMAD (both p<0.01) and negatively with percentage body fat (p<0.001). In males, 25OHD levels had a positive association with total body BMD and lean body mass (p=0.03 and p=0.01). Conclusions: 25OHD level is a determinant of peak BMD in both sexes. Vitamin D status was associated with body fat in females and with lean body mass in males.

Background : Plasminogen activator inhibitor-1 (PAI-1) has been considered as a cardiovascular risk factor, mainly because of its strong association with insulin resistance. Methods : To detect independent predictors of circulating PAI-1 levels in obese pediatric patients, we evaluated 86 subjects (mean age 10.7±2.8 years), 42 of whom were male (49%). Subjects were divided in two groups according to body mass index (BMI): obese subjects (n=61) and healthy non-obese controls (n=25). They were also divided by pubertal status. Besides anthropometric data, levels of PAI-1, leptin and biochemical markers of metabolic syndrome were measured. Results : The obese group had higher levels of PAI-1, leptin and biochemical markers of metabolic syndrome than non-obese controls (p<0.05). However, multivariate regression analysis showed that only puberty progression (p=0.005) and abdominal circumference/height index (p=0.002) remained independent predictors of PAI-1 levels. Conclusion : In pediatric obesity, fat mass accumulation, mainly of visceral fat, and puberty progression were related to high PAI-1 levels, which might in turn contribute to cardiovascular risk.

Background : Study results have varied when blood sugar control for subjects using a glargine basal-bolus insulin regimens (GBBIR) have been compared with those using continuous subcutaneous insulin infusion (CSII). Of 12 studies comparing GBBIR with CSII, six found improved glycemic control with CSII and six found no significant difference. These studies were often limited by small numbers of subjects and other study design parameters. Methods : We reviewed hemoglobin (Hb) A1c data for youths with type 1 diabetes (n=43) changing from conventional split mix insulin regimens (CSMIR) to GBBIR and subsequently to CSII at 3, 6 and 12 months after each transition. All subjects had a diabetes duration of at least 1 year before initiating GBBIR. Results : HbA1c levels at 3 months, 6 months and 1 year were not significantly different for GBBIR and CSII regimens. HbA1c increased significantly during GBBIR (p=0.036) and marginally during CSII (p=0.058) when 3-month and 1-year values were compared. Conclusions : We found no significant difference in glycemic control, as reflected by HbA1c, in youths with type 1 diabetes treated with GBBIR and CSII for up to 1 year. Blood sugar control waned by 12 months in both the GBBIR (p=0.036) and CSII (p=0.058) groups, which suggests that “burn out” qually affects those on each regimen. Additional investigation of glycemic variability and quality of life for those on GBBIR and CSII would be clinically relevant.

Permanent neonatal diabetes mellitus is a rare disorder usually presenting within the first few weeks or months of life. This disorder is genetically heterogeneous and has been associated with mutations in various genes. The genetic cause remains mostly unknown although several genes have been linked to this disorder. Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50%–60% of the patients. With genetic studies, we hope to increase our knowledge of neonatal diabetes, whereby new treatment models can become possible. Here, we defined a new variant of a known mutation, INS Exon 1-3 homozygous deletion, in two siblings diagnosed with permanent neonatal diabetes mellitus.

Background : HNF1A-MODY (MODY3) is a common subtype of autosomal dominant diabetes. Unlike HNF4-MODY where fetal macrosomia and early postnatal hyperinsulinemic hypoglycemia have been reported, a history of transient insulin overproduction has not been recognized in individuals with HNF1A-MODY yet. Case report : Here, we report a 40-year-old male patient with HNF1A mutation p.Arg272His (c.815G>A) with a history of fetal macrosomia (4750 g, 59 cm) and, at least, one attack of symptomatic hypoglycemia in childhood. Diabetes was subsequently diagnosed at 19 years. The proband’s daughter who developed diabetes at 16 years carries the same mutation, but her birth weight and length were in the upper normal range, and she never experienced hypoglycemic symptoms. Conclusion : The observation of fetal macrosomia and hypoglycemia in childhood is suggestive of a biphasic impact of the HNF1A mutation on β-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.

Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis, in utero fetal demise and neonatal distress. In some cases without hydrops, neurological signs occur in the first week of life and lead to death within 3 months. Less common signs of the disease are hepatosplenomegaly, ichthyosis, arthrogryposis and facial dysmorphy. We describe a preterm neonate with Gaucher disease homozygous for R463H mutation in GBA gene who showed severe neurologic signs in addition to refractory thrombocytopenia, hepatosplenomagaly, direct hyperbilirubinemia, facial dysmorphy and ichthyosiform skin abnormalities in addition to having thrombosis in portal and splenic veins possibly due to homozygosity for C677T mutation in MTHFR gene. To the best of our knowledge, this is the first case homozygous for the GBA R463H mutation resulting in Gaucher disease with a concomitant homozygous MTHFR C677T mutation.

A 15-year-old female presented to a pediatric emergency department with glycosuria, ketonuria, and hyperglycemia and was admitted with a presumed diagnosis of diabetes mellitus. The patient required no insulin therapy and only minor dietary modification to maintain euglycemia. Clinical examination and laboratory findings revealed a primary diagnosis of Graves’ hyperthyroidism with associated impaired glucose tolerance. Here, we review the mechanisms of thyrotoxicosis resulting in impaired glucose metabolism.

Wolfram syndrome is a progressive neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). The majority of cases are caused by mutations in the WFS1 gene. WFS1 is located at 4p16.1 and encodes wolframin, a transmembrane endoplasmic reticulum (ER) protein involved in the negative regulation of ER stress signalling. To date, over 120 WFS1 mutations have been described. In this study, we report a consanguineous family with three siblings affected by Wolfram syndrome. A homozygous single base pair deletion (c.877delC, L293fsX303) was found in the WFS1 gene in all three affected siblings.

Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency. Mutations in the ACTH receptor (melanocortin 2 receptor, MC2R ) or the MC2R accessory protein ( MRAP ) cause FGD types 1 and 2, respectively. A 2-year-old adopted Chinese girl presented with hypertonic seizures associated with hypoglycemia, skin hyperpigmentation, muscle weakness and mild jaundice. Hormonal analyses revealed high ACTH, low serum cortisol along with normal blood electrolytes. On hydrocortisone supplementation, the disease symptoms disappeared and the child recovered, although further episodes occurred with infection. To date, her physical and neurocognitive development progress is normal. A clinical diagnosis of FGD was given. We undertook MC2R and MRAP mutation screening. Two novel MC2R mutations were identified: p.D107G localized in the transmembrane region, predicted to be trafficking-competent but is unable to bind to ACTH, and p.R145C, situated in the second intracellular loop, predicted to be trafficking-defective.

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