Adherence to Mediterranean Diet, Dietary Salt Intake, and Susceptibility to Nephrolithiasis: A Case-Control Study.

Unhealthy dietary habits play a key role in the pathogenesis of nephrolithiasis (NL). The aims of this case-control study were to evaluate (i) the adherence to the Mediterranean Diet (MD) and the dietary salt intake in stone-forming patients (SF), (ii) the relationship occurring between MD adherence, salt intake and NL-related metabolic risk factors in SF, and (iii) the impact of combined high MD adherence and low salt intake on NL susceptibility. From 1 January 2018 to 31 December 2019, we recruited all SF consecutively referred to the Extracorporeal Shock Wave Lithotripsy (ESWL) center of Federico II University, and at least two control subjects without a personal history of NL, age-, sex-, and body mass index-matched to SF (NSF). All study participants were interviewed using the validated MEDI-LITE and MINISAL questionnaires. In an SF subgroup, the NL-related metabolic risk factors were also evaluated. SF showed a lower MD adherence and a higher salt intake compared with NSF. The NL susceptibility decreased by 36% [OR: 0.64 (0.59-0.70); p < 0.01] for each point of increase in MEDI-LITE score, while it increased by 13% [OR: 1.13 (1.03-1.25); p = 0.01] for each point of increase in MINISAL score. The SF prevalence was higher among subjects showing combined low MD adherence and high salt intake. In SF, the MEDI-LITE score directly correlated with 24 h-citraturia, whereas the MINISAL score directly correlated with urinary sodium and uric acid excretion. In conclusion, high MD adherence and low salt intake are associated with a reduced NL susceptibility, both separately and in combination.

Position statement on the diagnosis and management of congenital pituitary deficiency in adults: The French National Diagnosis and Treatment Protocol (NDTP).

Pituitary deficiency, or hypopituitarism, is a rare chronic disease. It is defined by insufficient synthesis of one or more pituitary hormones (growth hormone, TSH, ACTH, LH-FSH, prolactin), whether or not associated with arginine vasopressin deficiency (formerly known as diabetes insipidus). In adult patients, it is usually acquired (notably during childhood), but can also be congenital, due to abnormal pituitary development. The present study focuses on congenital pituitary deficiency in adults, from diagnosis to follow-up, including special situations such as pregnancy or the elderly. The clinical presentation is highly variable, ranging from isolated deficit to multiple deficits, which may be part of a syndromic form or not. Diagnosis is based on a combination of clinical, biological (assessment of all hormonal axes), radiological (brain and hypothalamic-pituitary MRI) and genetic factors. Treatment consists in hormonal replacement therapy, adapted according to the period of life and the deficits, which may be progressive. Comorbidities, risk of complications and acute decompensation, and the impact on fertility and quality of life all require adaptative multidisciplinary care and long-term monitoring.

Integrated Management of an Adult Patient with Mucopolysaccharidosis type IVA: A Case Report with a Six-Year Follow-up.

Mucopolysaccharidosis type IVA (MPS-IVA) is a rare lysosomal storage disease caused by N-acetylglucosamine-6-sulfate-sulfatase enzyme deficiency. MPS-IVA patients show severe extra-skeletal and skeletal manifestations, featured by bone pain and deformities, frailty fractures and early onset osteoporosis. The enzyme replacement therapy (ERT) with elosulfase-α stabilizes the MPS-IVA extra-skeletal manifestations but does not significantly improve MPS-IVA skeletal manifestations. We administered an integrated therapy to an MPS-IVA 41-year-old male patient, composed of zoledronic acid, cholecalciferol and a normocalcemic (calcium intake ≥1 g/day), hyposodic (sodium intake ≤5 g/day), and normocaloric diet (bone-diet), other than ERT. During the six-year follow-up, the patient did not develop any adverse events, obtaining an improvement of bone mineral density and quality of life. Given our results, we propose this integrated treatment (i.e. ERT, zoledronic acid, cholecalciferol, and bone diet) in the management of MPS-IVA adult patients. LEARNING POINTS: Mucopolysaccharidosis type IVA (MPS-IVA) is a genetic, rare, and degenerative spondylo-epiphyso-metaphyseal dysplasia characterized by extra-skeletal and skeletal manifestations. The latter impacts on MPS-IVA patient daily activities, and enzyme replacement therapy has a poor efficacy in improving skeletal involvement.The proposed integrated management with enzyme replacement therapy, zoledronic acid, cholecalciferol and bone diet improve both bone mineral density and the prognosis quoad valetudinem of our MPS-IVA patient.

Clinical Characteristics of Malignant Phosphaturic Mesenchymal Tumor Causing Tumor-Induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal tumor (PMT). PMTs are usually benign neoplasms but some of them show malignant characteristics. OBJECTIVE: The aim of this study was to compare the clinical characteristics of benign and malignant PMTs inducing TIO. METHODS: On March 31, 2023, we performed a systematic review of individual patient data analysis in Medline, Google Scholar, Google book, and Cochrane Library using the terms "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia," with no language restrictions and according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. RESULTS: Overall, we collected data from 837 patients with TIO in which the diagnosis of benign and malignant PMT was specified. Of them, 89 were affected by malignant PMT and 748 by benign PMT. Patients with malignant PMTs were younger and presented bone pain, functional impairment, and bone deformities more frequently. Malignant PMTs showed higher values of intact FGF23 and a higher mortality rate. CONCLUSION: The study results identify the clinical characteristics of patients with malignant TIO, permitting the early identification of patients with PMT at increased risk of malignancy. This may significantly improve the diagnostic approach to disease. Further experimental studies are mandatory to clarify the role of FGF23 in the pathogenesis of malignancy in PMTs.

Venous thromboembolism and major bleeding in severe and critical COVID-19 hospitalized patients.

Venous thromboembolism (VTE) and major bleeding (MB) are life-threatening complications described in COVID-19 hospitalized patients and they can be considered as two sides of the same coin. This retrospective study aims to evaluate the risk factors for VTE and MB in COVID-19 patients admitted to two Italian hospitals. The medical records of all COVID-19 patients (males 139; 62.3%, mean age 67.2±13.6 years, body weight 88.2±20.6 kg) hospitalized from March 11th to July 31st, 2020 to the Federico II University Hospital and to Sea Hospital, Naples, Italy, were analyzed. The COVID-19 patients were classified into four groups: COVID-19 patients developing VTE and/or MB, COVID-19 patients developing only VTE, COVID-19 patients developing only MB, and COVID-19 patients not developing neither VTE nor MB. During the hospitalization, 53 COVID-19 patients (24.7%; males 40; 75.5%, mean age 67.2±13.6 years, weight 88.2±20.6 kg) developed VTE, 33 COVID-19 patients (15.3 %; males 17; 51.5, mean age 67.3±14.9 years, weight 74.1±14.3 kg) developed MB, and 129 COVID-19 patients not developed neither TVP nor MB. No parameters to identify severe COVID-19 complicated by VTE and/or MB were found. However, some clinical and biochemical parameters can be evaluated to predict the risk of MB in order to modify the treatment and take prompt action to reduce mortality.

Low Potassium Intake: A Common Risk Factor for Nephrolithiasis in Patients with High Blood Pressure.

Hypertension (Htn) is a crucial cause of cardio-vascular and chronic kidney disease. Moreover, it is an independent risk factor for nephrolithiasis (NL). A diet rich in vegetables and fruits is indicated for both Htn and NL prevention, and the 24-h urinary potassium excretion can be used as a warning light for adherence. The aim of this study is to demonstrate the association between urinary potassium excretion and recurrent nephrolithiasis among patients affected by Htn. We have analyzed medical records of 119 patients affected by Htn and NL (SF-Hs) referring to Bone and Mineral Metabolism laboratory and 119 patients affected by Htn but without NL (nSF-Hs) referring to Hypertension and Organ Damage Hypertension related laboratory, both in Federico II University of Naples. The potassium 24-h urinary levels in SF-Hs were significantly lower compared to nSF-Hs. This difference was confirmed by the multivariable linear regression analysis in the unadjusted model and adjusted model for age, gender, metabolic syndrome, and body mass index. In conclusion, a higher potassium urinary excretion in 24-h is a protective factor against NL in patients affected by Htn and dietary interventions can be considered for kidney protection.

[Child and adolescent obesity: what assessment?] / Obésité de l'enfant et de l'adolescent : quel bilan ?

CHILD AND ADOLESCENT OBESITY: WHAT ASSESSMENT? The prescription of laboratory tests or imaging in obese children and adolescents should be guided by the clinical features. It recognizes two main objectives: to eliminate a differential diagnosis (in particular, due to hypercorticism or hypothyroidism) and to detect the presence of comorbidities, assuming that some complications of obesity in adults can be sometimes present even in young age.

OBÉSITÉ DE L'ENFANT ET DE L'ADOLESCENT : QUEL BILAN ? La prescription d'examens complémentaires chez un enfant et un adolescent en situation d'obésité doit être guidée par les éléments cliniques. Elle reconnaît deux objectifs principaux : établir un diagnostic différentiel de l'obésité commune (en particulier un hypercorticisme ou une hypothyroïdie) et dépister la présence d'éventuelles comorbidités, sachant que certaines complications de l'obésité bien connues chez l'adulte peuvent parfois être présentes depuis le plus jeune âge.

25-Hydroxy-Vitamin D and Risk of Recurrent Stroke: A Dose Response Meta-Analysis.

Stroke recurrence significantly improves the prognosis quoad vitam et valetudinem of patients with a first ischemic or haemorrhagic stroke. Other than in bone and skeletal metabolism, vitamin D is involved in the pathogenesis of cardiovascular disorders. This meta-analysis was performed to evaluate the relationship between 25OH-vitamin D [25(OH)D] levels at the first stroke and the stroke recurrence. To 31 July 2022, four prospective studies were identified. The potential non-linear relationship was evaluated by modelling 25(OH)D, using restricted cubic splines of 25(OH)D distribution. The pooled estimated risk (and 95% CI) of the recurrence of stroke, comparing the highest and the lowest levels, was assessed using a random-effect model. A non-linear association was found by dose-response analysis. This study found that 25(OH)D levels at the first stroke ≥9.3 ng/mL were associated with a lower risk of stroke recurrence, compared with 25(OH)D levels ≤8.5 ng/mL. In the pooled analysis, higher 25(OH)D levels at the first stroke significantly reduce the risk of stroke recurrence, with a significant heterogeneity among studies. In conclusion, 25(OH)D levels ≤8.5 ng/mL at the first stroke are significantly associated with a higher risk of recurrent stroke.

Iodine Requirements in Pediatrics: From Fetal Life to Adolescence.

The aim of this mini-review is to present the current knowledge on iodine requirements in developmental age, from conception to adolescence. It is based on the analysis of updated national and international guidelines on iodine intake and the prevention of iodine deficiency. Health policy initiatives carried out in industrialized countries in previous decades have led to a dramatic improvement in nutritional iodine status in the general population. However, the prevention of iodine deficit continues to be a concern, especially for vulnerable categories, like adolescents and pregnant women.

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study.

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Turner syndrome: French National Diagnosis and Care Protocol (NDCP; National Diagnosis and Care Protocol).

Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40-50%) and the 45,X/46,XX mosaic karyotype (15-25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.

Tumor-induced Osteomalacia: A Systematic Review and Individual Patient's Data Analysis.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. EVIDENCE ACQUISITION: On June 26, 2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia." There were no language restrictions. This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. EVIDENCE RESULTS: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared with TIO women. The TIO-causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO-causing neoplasms were equally located in bone and soft tissues; the latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in > 90% of patients). Promising nonsurgical therapies are treatments with burosumab in TIO patients with elevated fibroblast growth factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. CONCLUSION: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located in soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising nonsurgical therapies.

Current clinical management of constitutional delay of growth and puberty.

BACKGROUND: Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences. MAIN TEXT: A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended. CONCLUSION: Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.

Age at diagnosis in patients with chronic congenital endocrine conditions: a regional cohort study from a reference center for rare diseases.

BACKGROUND: For chronic congenital endocrine conditions, age at diagnosis is a key issue with implications for optimal management and psychological concerns. These conditions are associated with an increase in the risk of comorbid conditions, particularly as  it concerns growth, pubertal development and fertility potential. Clinical presentation and severity depend on the disorder and the patient's age, but diagnosis is often late. OBJECTIVE: To evaluate age at diagnosis for the most frequent congenital endocrine diseases affecting growth and/or development. PATIENTS AND METHODS: This observational cohort study included all patients (n = 4379) with well-defined chronic congenital endocrine diseases-non-acquired isolated growth hormone deficiency (IGHD), isolated congenital hypogonadotropic hypogonadism (ICHH), ectopic neurohypophysis (NH), Turner syndrome (TS), McCune-Albright syndrome (MAS), complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD)-included in the database of a single multisite reference center for rare endocrine growth and developmental disorders, over a period of 14 years. Patients with congenital hypothyroidism and adrenal hyperplasia were excluded as they are generally identified during neonatal screening. RESULTS: Median age at diagnosis depended on the disease: first year of life for GD, before the age of five years for ectopic NH and MAS, 8-10 years for IGHD, TS (11% diagnosed antenatally) and CAIS and 17.4 years for ICHH. One third of the patients were diagnosed before the age of five years. Diagnosis occurred in adulthood in 22% of cases for CAIS, 11.6% for TS, 8.8% for GD, 0.8% for ectopic NH, and 0.4% for IGHD. A male predominance (2/3) was observed for IGHD, ectopic NH, ICHH and GD. CONCLUSION: The early recognition of growth/developmental failure during childhood is essential, to reduce time-to-diagnosis and improve outcomes.

Obesity-Related Hypertension in Pediatrics, the Impact of American Academy of Pediatrics Guidelines.

The prevalence of primary hypertension in pediatric patients is increasing, especially as a result of the increased prevalence of obesity in children. New diagnostic guidelines for blood pressure were published by the American Academy of Pediatrics (AAP) in 2017 to better define classes of hypertension in children. The aim of our study is to evaluate the impact of new guidelines on diagnosis of hypertension in pediatrics and their capacity to identify the presence of cardiovascular and metabolic risk. Methods: Retrospective clinical and laboratory data from 489 overweight and obese children and adolescents were reviewed. Children were classified according to the 2004 and 2017 AAP guidelines for systolic and diastolic blood pressure. Lipid profile and glucose metabolism data were recorded; triglyceride/HDL ratio (TG/HDL) was calculated as an index of endothelial dysfunction. Hepatic steatosis was detected using the ultrasonographic steatosis score. Results: Children with elevated blood pressure increased from 12.5% with the 2004 AAP to 23.1% with the 2017 AAP criteria (p < 0.001). There was a statistically significant increase in children with high blood pressure in all age groups according to the new cut-off values. Notably, the diagnosis of hypertension according to 2017 AAP criteria had a greater positive association with Hepatic Steatosis (rho 0.2, p < 0.001) and TG/HDL ratio (rho 0.125, p = 0.025). Conclusions: The 2017 AAP tables offer the opportunity to better identify overweight and obese children at risk for organ damage, allowing an earlier and more impactful prevention strategy to be designed.

Obesity in Pediatric-Onset Multiple Sclerosis: A French Cohort Study.

OBJECTIVE: To study the link between a high body mass index (BMI) in childhood and the occurrence of pediatric-onset multiple sclerosis (POMS) and to compare, within the MS population, the clinical-radiologic-biological characteristics, according to BMI. METHODS: A case-control study comparing BMI data of 60 patients with POMS (39 girls and 21 boys) at Bicêtre Hospital with that of 113 non-neurologic controls NNCs (68 girls and 45 boys) and 18,614 healthy controls HCs (9,271 girls and 9,343 boys) was performed. Crude BMI (cBMI), residual BMI (rBMI = measured BMI - expected BMI for age), z-score (rBMI/SD), and adult equivalent categories (International Obesity Task Force ≥25 = overweight, ≥30 = obese) were assessed. RESULTS: In boys, cBMI and rBMI were significantly higher in patients with POMS compared with NNCs (cBMI: +2.9; rBMI: +2.95, p < 0.01) and HCs (cBMI: +2.04, p < 0.01). In girls, cBMI or rBMI did not differ between POMS and NNCs patients (cBMI p = 0.4; rBMI p = 0.44) but with HCs (cBMI +0.99, p < 0.01). CSF inflammatory markers increased with BMI in prepubertal patients (p < 0.01), whereas vitamin D level at diagnosis was lower in boys with higher BMI (p = 0.016). Increased BMI was not associated with clinical and radiologic disease characteristics. CONCLUSIONS: Overweight and obesity are more frequently observed at diagnosis, particularly in boys with POMS compared with non-neurologic controls and French HCs. Moreover, BMI is related to initial inflammation in the CSF in prepubertal patients with POMS suggesting an interaction between excess body fat, sexual hormones, and POMS occurrence.

Trends in metabolic bariatric surgery in adolescents in France: a nationwide analysis on an 11- year period.

BACKGROUND: As the prevalence of obesity in adolescents has reached an alarming level of 16%, the rate of metabolic bariatric surgery (MBS) in this population is also rising in several countries. OBJECTIVES: This study aimed to compare the trends in types of MBS, short-term safety, and revisional rates, in younger adolescents aged < 18 years, compared with older adolescents (aged 18-19 yr) and adults aged >20 years. SETTING: Clinical research center, general hospital in France. METHODS: Using a national administrative database (Programme de Médicalisation des Systèmes d'Information [PMSI]), data regarding all patients undergoing MBS between 2008 and 2018 in France were examined. Demographic parameters, body mass index (BMI), co-morbidities, types of surgery, early complications, and long-term revisional rates were analyzed, comparing younger adolescents (<18 yr), older adolescents (18-19 yr), and adults (≥20 yr). RESULTS: The number of bariatric procedures in adolescents initially increased from 59 in 2008 to 135 in 2014, and then progressively declined to 56 procedures in 2018. Adjustable gastric banding (AGB) decreased from 83.1% (n = 49) of procedures to 32.1% (n = 18) of procedures during the study period, while sleeve gastrectomy (SG) increased from 6.8% (n = 4) to 46.4% (n = 26). In the early postoperative period, younger adolescents undergoing MBS experienced fewer episodes of reoperation (1.0% versus 1.3% in older adolescents and 2.6% in adults, P < .001) and intensive care unit (ICU) stays (.2% versus .2% in older adolescents and .6% in adults, P < .001), and no deaths were observed in younger adolescents (.02% in older adolescents and .1% in adults, P = .18). At 10 years, the AGB removal rate was lower in younger adolescents (24.8%) compared with that in older adolescents (29.6%) and adults (50.3%, P < .001). Similarly, rates of revisional surgery after SG were different in the 3 groups: 2.9%, 4.6% and 12.2% in younger adolescents, older adolescents, and adults, respectively. CONCLUSION: Despite significantly lower early complication rates and long-term revisional rates in young adolescents (<18 yr), we observed a progressive decrease in the utilization of MBS in this population in France, compared with adults (≥20 yr) and older adolescents (18-19 yr).

Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity.

CONTEXT: Unlike homozygous variants, the implication of heterozygous variants on the leptin-melanocortin pathway in severe obesity has not been established. OBJECTIVE: To describe the frequency, the phenotype, and the genotype-phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity. METHODS: In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities. RESULTS: The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI. CONCLUSION: Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.