Less ready for adulthood?-Turner syndrome has an impact on transition readiness.

OBJECTIVE: Young women with Turner syndrome (TS) are known to be at risk for loss to medical follow-up. Recent literature indicates that there are disparities regarding transition readiness between different chronic conditions. So far, studies in young women with TS investigating their transition readiness compared to youths with other chronic conditions with no or minor neurocognitive challenges have not been reported. METHODS: Patients (n = 52), 26 patients with Turner syndrome (mean age 17.24 ± 2.10) and 26 controls with type 1 diabetes or a rheumatic disease (mean age 17.41 ± 2.44), were recruited from specialized paediatric endocrine outpatient clinics. The Transition Readiness Assessment Questionnaire TRAQ-GV-15 was used to compare transition readiness scores between TS and controls. In addition, information on individual handling of the questionnaire was obtained. Descriptive statistics and nonparametric methods were used to analyse the data. RESULTS: Significant differences for transition readiness scores were found between the two study groups. The global TRAQ-GV-15 score was significantly lower for females with TS. In particular, subscale 1 'autonomy' of the TRAQ-GV-15 showed lower scores in patients with TS. Patients with TS needed significantly more help and more time to complete the questionnaire. CONCLUSION: Special attention should be given to young women with Turner syndrome in the preparation for the transitional phase. By incorporating the assessment of transition readiness specialists will find it easier to identify underdeveloped skills and knowledge gaps in their patients. Unless a multidisciplinary young adult clinic is established, an older age than 18 years at transfer to adult endocrine care might be beneficial.

Weight and body mass index (BMI): current data for Austrian boys and girls aged 4 to under 19 years.

BACKGROUND: BMI reference charts are widely used to diagnose overweight, obesity and underweight in children and adolescents. AIM: To provide up-to-date national reference values for Austria. METHODS: A cross-sectional sample of over 14 500 children and adolescents (4-19 years) stratified by provinces according to age- and sex-specific population proportions was drawn via schooling institutions (kindergartens, schools and vocational colleges). The generalized additive models for location, scale and shape were used for a flexible estimation of percentile curves. RESULTS: Austrian boys and girls have higher average weight compared with previous prevalence data. BMI centiles matching BMI values at age 18 years, which are used for defining thinness, overweight and obesity in adults, were calculated. In Austria, using reference values as thresholds, ∼18% of boys and 12% of girls are overweight (with thresholds passing through BMI 25.00-29.99 kg/m(2) in adults) and 5% of boys and 3% of girls are obese (with thresholds passing through BMI ≥30.00 kg/m(2) in adults). CONCLUSION: Overweight and obesity are common in Austria and their prevalence is increasing (using the same IOTF reference for international comparison). Up-to-date national BMI reference values are provided to classify children and adolescents according to the proposed overweight and obesity thresholds.

Austrian height and body proportion references for children aged 4 to under 19 years.

BACKGROUND: Previous studies have demonstrated differences between national and the WHO reference curves in children older than 5 years. Moreover, reference curves for body proportions (sitting height, subischial leg length and their ratio) based on state-of-the-art statistics are not available. AIM: To develop reference curves for height and body proportions for use in Austria and compare the curves with WHO reference curves. To estimate and statistically investigate extreme percentiles. SUBJECTS AND METHODS: A sample of ∼14 500 children between 4-19 years of age was drawn via schooling institutions, stratified by provinces according to age- and sex-specific population proportions. GAMLSS models were used for a flexible estimation of percentile curves. RESULTS AND CONCLUSIONS: After the age of 5 years national reference curves are more suitable than the WHO reference curves for clinical use in Austria. These height curves are very similar to the German reference curves published recently. Therefore, these reference curves for criteria of body proportions are recommended for use in other populations. Further validation studies are needed to establish whether the recently recommended -2.5 and -3.0 SD for height are a sensitive and specific cut-off in the diagnostic work-up for children with a suspected growth disorder using this new Austrian height chart.

Molecular karyotyping as a relevant diagnostic tool in children with growth retardation with Silver-Russell features.

OBJECTIVE: To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes. STUDY DESIGN: We performed molecular karyotyping in 41 patients with SRS or SRS-like features without known chromosome 7 and 11 defects using the Affymetrix SNP Array 6.0 system (Affymetrix, High Wycombe, United Kingdom). RESULTS: In 8 patients, pathogenic copy number variations with sizes ranging from 672 kb to 9.158 Mb were identified. The deletions in 1q21, 15q26, 17p13, and 22q11 were associated with known microdeletion syndromes with overlapping features with SRS. The duplications in 22q13 and Xq25q27 represent unique novel copy number variations but have an obvious influence on the phenotype. In 5 additional patients, the pathogenetic relevance of the detected variants remained unclear. CONCLUSION: Pathogenic submicroscopic imbalances were detectable in a significant proportion of patients with short stature and features reminiscent of SRS. Therefore, molecular karyotyping should be implemented in routine diagnostics for growth-retarded patients with even slight dysmorphisms suggestive for SRS.

SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.

N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in the steroid 5alpha-reductase type 3 (SRD5A3) gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway for dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation.

Refining clinical phenotypes in septo-optic dysplasia based on MRI findings.

Septo-optic dysplasia (SOD) is a heterogeneous brain midline anomaly associated with ophthalmological, endocrinological, and/or neurodevelopmental symptoms. The clinical phenotype correlates with abnormal brain magnetic resonance imaging (MRI) findings. However, variations of the septum pellucidum (SP) appearance and their clinical impact have not been studied in depth. Sixty-eight patients with optic nerve hypoplasia (ONH) were investigated for the presence of associated SP anomalies and correlations between clinical findings and their MRI abnormalities established. Thirty patients had either complete (n = 22) or partial (n = 8) absence of the SP. Pituitary hormone deficiencies were present in 64% or 25% of the cases, respectively. Neurological symptoms did not occur in patients with SP remnants or unilateral ONH. Hippocampus abnormalities (43%) that have not been described before in SOD and falx abnormalities (17%) correlated significantly with neurological symptoms and developmental delay (p < 0.05 and p < 0.01, respectively). Maternal age at birth was low (21.2 years) and drug abuse during pregnancy was reported in 27% of the patients. Twelve patients with pituitary anomaly and ONH but normal SP showed similar clinical and MRI features, and were classified as SOD-like. The remaining 26 patients were not assigned to SOD. We conclude that unilateral ONH and SP remnants are associated with a milder SOD phenotype. Hippocampus abnormalities and falx abnormalities seem to constitute important features of severe clinical disease, irrespective of SP appearance. Our anamnestic data support the hypothesis of vascular disruption during embryogenesis.

Death in two female Prader-Willi syndrome patients during the early phase of growth hormone treatment.

UNLABELLED: Reports on sudden death in Prader-Willi syndrome (PWS) patients after the start of growth hormone (GH) treatment have been published recently. We observed a 4.7-y-old girl who showed a continuous increase in pulmonary artery pressure and died of cardiorespiratory failure 7 wk after GH therapy had been initiated, and a 9.3-y-old girl with additional trisomy 21 who died during a minor respiratory infection 6 mo after GH had been started. Both patients were overweight (weight for height 127% and 224%, respectively). GH-induced fluid retention may have occurred in the younger girl. In contrast to the reported cases, our PWS patients were female. CONCLUSION: Our cases illustrate the difficulty of differentiation between possible GH side effects and the natural course of disease, in particular with respect to obesity-related comorbidity and mortality.