The characteristics of scoliosis were investigated in a large cohort of children and adults with Prader–Willi syndrome (PWS), analysing the role of age, gender, puberty, body mass index (BMI), genotype and growth hormone therapy (GHT) on its onset and severity. A retrospective cross-sectional study was performed in 180 patients with genetically confirmed PWS (96 females), aged 17.6 ± 12 years. Eighty-five subjects (47%) were obese. One hundred and fifty subjects (83.3%) were on GHT, while 30 patients had never been treated. Overall, 150 subjects (83.3%) were affected by scoliosis, 80.2% of children and adolescents and 87.8% of adults. A mild degree of scoliosis was observed in 58 patients (38.7%), moderate in 43 (28.7%) and severe in 49 (32.6%). Median age at diagnosis of scoliosis was 6.3 years, while the severe forms were diagnosed earlier (median age: 3.8 years). The cumulative probability at 5 years of age was equal to 0.403 and almost doubled at 15 years. No significant associations were found between scoliosis and genotype, gender, pubertal stage, GHT and BMI. A corset was prescribed to 75 subjects (50%) at a median age of 7.5 years, while 26 subjects (17.3%) underwent surgery at a median age of 13.1 years. Our data indicate that scoliosis is one of the major concerns for PWS patients that increases with age, and therefore suggest the need for regular systematic monitoring of spinal deformity from paediatric age.

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the ”Bambino Gesù Children Hospital”, a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = −0.31, p < 0.001, BCa 95% −0.38, −0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = −0.33, p = 0.008, BCa 95% −0.53, −0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = −0.003 (−0.007, −0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (p_trend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and <0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and <0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.

Childhood obesity has been correlated with coronary heart disease, but the correlation with microvascular disease remains unclear. The retinal microcirculation is affected early in the process of atherosclerosis and it offers the opportunity to indirectly study the effects of obesity on small brain vessels. Insulin-like growth factor 1 (IGF-I) is involved in angiogenesis and it has a crucial role in retinal vascularization. A single-centre cross-sectional study was performed in 268 children and adolescents (116 males; mean age 13.03 ± 1.9 years,) with overweight/obesity, in order to identify risk factors for early retinopathy. Nine patients (3.3%) showed signs of retinopathy, defined as arteriovenous crossings and/or papilledema. Body mass index and fat mass, analysed by Dual X-ray Absorptiometry, were not different in patients with or without retinopathy. Patients with retinopathy were pubertal and showed higher waist circumference (107.78 ± 15.83 versus 99.46 ± 10.85 cm; p: 0.027), waist circumference/height ratio (0.66 ± 0.07 versus 0.62 ± 0.05; p: 0.04) and IGF-I SDS (0.03 ± 1.3 versus − 0.66 ± 0.9; p: 0.04). Multivariate analysis (after correction for sex, age, family history of type 2 diabetes mellitus, obesity, cardiovascular disease, hypertension and dyslipidaemia) showed that waist circumference/height ratio and IGF-I SDS were the only variables independently correlated with the presence of retinopathy. Retinal vascular changes may become evident as an early complication of overweight and obesity, even during childhood and adolescence. Relatively high levels of IGF-I during this phase may act as an additional risk factor for microvascular damage. The screening for retinopathy should be proposed to all children and adolescents with overweight/obesity.

Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

Background: Currently, there is a lack of data regarding the reliability of different anthropometric, instrumental, and biochemical indexes in detecting metabolic syndrome (MetS) in pediatric patients with Prader–Willi syndrome (PWS). Therefore, this study aimed to compare the accuracy of different indices to identify the simplest and most accurate predictor of MetS in this at-risk population. Methods: We conducted a multicenter study involving 124 children and adolescents with PWS (61 males and 63 females), aged 13.6 ± 3.7 years. For each participant, we assessed all components of MetS, defined according to either the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study or the International Diabetes Federation (IDF) criteria, based on age. The following indexes were calculated: Body Mass Index (BMI), BMI standard deviation score (BMI-SDS), tri-ponderal mass index, body mass fat index, fat mass index, fat-free mass index, body shape index, visceral adiposity index, waist-to-height ratio, cardiometabolic index, total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, and triglycerides/HDL-C (TG/HDL-C) ratio. Results: MetS was identified in 24 subjects (9 females and 15 males), representing 19.4% of the sample. When comparing the receiver operating characteristic (ROC) curves, the TG/HDL-C ratio and cardiometabolic index demonstrated significantly better performance than the other indices in detecting MetS, with no difference between the two. As a result, we focused on the TG/HDL-C ratio since it is the simplest measure, requiring no additional anthropometric data compared to the cardiometabolic index. Additionally, applying age- and gender-specific thresholds can further improve its accuracy. Conclusions: The TG/HDL-C ratio, which requires only two standard biochemical markers, provides the same accuracy as more complex indexes in detecting MetS in children and adolescents with PWS, making it the optimal predictor for MetS in this population.

Introduction: Hypothalamic–pituitary anomalies are well proven in Prader–Willi syndrome (PWS). In this context, it has been previously reported that central adrenal insufficiency (CAI) may be part of the PWS phenotype. However, the diagnostics of CAI is critical and debated, due to the lack of fully reliable tests. Several studies have looked at the clinical usefulness of the low dose (1 μg) short Synacthen test (LDSST) compared to the conventional dose (250 μg) test (SDSST) in patients with pituitary disease. Actually, the dose used in the SDSST is considered supraphysiological and might produce a deceivingly adequate cortisol (F) response. Nevertheless, other reports suggested no difference between the LDSST and SDSST in patients with multiple pituitary hormone deficiency. Objective: To compare the F response to both LDSST and SDSST in a large group of PWS adults. Methods and patients: Forty-six PWS subjects, 23 males, aged 18–41 years, underwent LDSST and SDSST. In each test blood samples for F determination were taken at 0 and 30 min. A F peak >18.1 μg/dl was considered to be a normal response. Results: The mean peaks of F after LDSST and SDSST were 22.2±0.7 μg/dl (mean±S.E.) and 22.7±0.7 μg/dl respectively (P=0.8). The average increase of F from baseline was 10.4±0.7 μg/dl (LDSST) and 12.1±0.7 μg/dl (SDSST) (P=0.02). The LDSST and SDSST produced 32 normal and two abnormal concordant results. Seven patients who passed the SDSST failed the LDSSD, while five subjects failed the SDSST but passed the LDSSD. Conclusions: F responses to different SSTs were discordant in 26.1% of our cases. In this light, further research is needed to identify the more reliable test for diagnosing CAI in these patients – e.g. an ITT or overnight metyrapone test on those who had abnormal response to LDSST or SDSST in order to confirm the presence of CAI.