Introduction: Oral health is a key component of overall health, yet it is often overlooked in children with severe or complex obesity. This study aimed to describe the oral health of children with severe or complex obesity and to explore the association between markers of glucose metabolism and gingivitis. Methods: This cross-sectional analysis included patients aged <18 years who received care management at a paediatric specialised obesity centre (November 2020-December 2024, France). Oral health data were collected using a standardised questionnaire (preventive habits, quality of life) and a clinical examination (dental caries, gingivitis). Glucose metabolism markers (fasting glucose, insulin, HbA1c and triglycerides/HDL-c ratio) were retrieved from medical records and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Associations with gingivitis were assessed using confounder-adjusted logistic regression. Results: One hundred thirty-two participants were included (52% females, 58% aged ≥12 years). Just over half reported brushing twice a day or more, 33% had at least 1 untreated dental caries and 44% had gingivitis. Additionally, 19% reported oral pain and 17% aesthetic concerns. Participants exhibited altered glucose metabolism, especially adolescents; however, no association was observed between markers of glucose metabolism and gingivitis. Conclusion: This study highlighted the need to improve access to preventive oral health measures and care for young individuals with severe or complex obesity. However, alterations in glucose metabolism did not appear to be associated with gingival inflammation. Clinical relevance: Children with severe or complex obesity have high oral health needs; integrating dental care into multidisciplinary management may help prevent caries, gingivitis and related quality-of-life impairments.

Sideroflexin 4 (SFXN4) is a transmembrane protein located in the inner membrane of the mitochondria. SFXN4 is also thought to be involved in the formation of iron-sulphur centres. Deleterious bi-allelic variants of the SFXN4 gene have been reported in only 3 patients, with a phenotype including intellectual disability and macrocytic anaemia. We describe here a patient carrying pathogenic variants of SFXN4, associated with a non-anaemic sideroblastic macrocytosis and a complex I deficiency.

BACKGROUND:Children carrying germline RET mutations associated with multiple endocrine neoplasia type 2 (MEN2) are at high risk of developing medullary thyroid carcinoma (MTC). Prophylactic-intent thyroidectomy is recommended during childhood to prevent progression to advanced disease. Genotype-based recommendations combined with calcitonin measurements allow more individualized surgical timing. However, performing thyroidectomy at very young ages may expose children to long-term morbidity, particularly permanent hypoparathyroidism. METHODS:We conducted a retrospective national multicenter cohort study within the French Groupe d'Étude des Tumeurs Endocrines, including children younger than 15 years who underwent prophylactic-intent total thyroidectomy between 2010 and 2020 in the absence of clinically apparent structural disease. Data collected included RET genotype, age at surgery, preoperative calcitonin values interpreted relative to each laboratory's upper limit of normal, surgical procedures performed, histopathologic findings, postoperative complications, and clinical status at last follow-up. RESULTS:Sixty-four children (61 MEN2A, 3 MEN2B) underwent surgery at a median age of 4.6 years (interquartile range [IQR] = 3.2-8.3 years). Preoperative calcitonin was elevated in 44% of evaluable patients. Histopathology demonstrated C-cell hyperplasia in 52% and micro-MTC in 34%, while lymph node metastases were rare (3%). After a median follow-up of 6 years (IQR = 2.4-8.5 years), no patient had persistent structural disease. One patient had persistent moderate biochemical disease without structural evidence of MTC, although follow-up duration limits definitive long-term oncologic outcomes. Postoperative morbidity was notable: hypoparathyroidism occurred in 31% of patients and was permanent in 16%, predominantly among children operated before age 5 years. CONCLUSIONS:In this national contemporary cohort, prophylactic-intent thyroidectomy in pediatric MEN2 was associated with excellent short-term oncologic outcomes but also with a substantial rate of permanent hypoparathyroidism, particularly in very young children. These findings underscore the importance of multidisciplinary evaluation of both the timing and extent of surgery in expert centers.

Introduction: Isolated growth hormone deficiency (IGHD) involves multiple genes, yet characterization of its mutational landscape and genotype-phenotype correlations remains limited. The aim of this study was to analyze a large cohort of patients with genetic IGHD and describe associated genotypes and phenotypes. Methods: Descriptive study of IGHD patients with an identified genetic cause was referred for targeted NGS panel analysis through the GENHYPOPIT network between 2017 and 2024, and complementary targeted family analysis. Results: Among 205 patients with IGHD, 23 (11.2%) had a pathogenic (P) or likely pathogenic (LP) variant. The average age at diagnosis was 3.9 years, and 47% of patients had pituitary hypoplasia. Seventy percent of variants were in GH secretion genes, 39% in GH1, mostly with autosomal dominant transmission, 13% in GHRHR, and 18% in GHSR, with autosomal dominant or recessive inheritance and incomplete penetrance. Variants in genes involved in pituitary development were rarer (30% of variants). The most commonly affected pituitary development gene was GLI2 (13%). GLI2 variants were always associated with pituitary stalk interruption syndrome. The remaining variants were in POU1F1 (9%), HESX1 (4%), and SOX3 (4%). We report 10 new P or LP variants. Family analyses (n = 30) broadened the genotype-phenotype correlation, identified de novo variants, as well as the first ever reported case of GH1 mosaicism. Conclusion: Our study broadens the spectrum of genetic variations associated with IGHD. In most cases, the implicated gene is involved in GH secretion, but our results highlight that IGHD can also be caused by genes involved in pituitary development. These findings confirm the importance of genetic analysis in IGHD, to improve patient management and genetic counselling.

Abstract MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory capacity, however, maintained over time, and extra-pancreatic manifestations in some patients. Its prevalence has been estimated 0.6% to 6.5% of all diabetes in Europe and the USA. Pathogenic variants in the genes encoding glucokinase or transcription factors HNF1A or HNF4A are responsible for the majority of cases of monogenic forms of diabetes referred to as MODY. The objective of the French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins) dedicated to GCK-MODY (formerly MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) is to provide to health professionals a guide for optimal management and care of patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Thorough analysis of personal and family history, clinical examination and biochemical testing are key to raise the diagnosis, which has to be confirmed by molecular analysis. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. Overall, the management of patients with MODY requires the collaboration of several health care providers.

Introduction L’augmentation de l’incidence du diabète de type 1 de l’enfant et de l’adolescent constitue un enjeu d’organisation des prises en charge pour les équipes pédiatriques spécialisées. Le suivi recommandé est d’une consultation tous les 3 mois et un bilan annuel pluriprofessionnel. Notre étude a pour but de décrire le suivi sur un an d’enfants et d’adolescents diabétiques connus de l’équipe pour visualiser les organisations proposées. Méthodes Le suivi d’un an est décrit à partir de 7 contacts avec l’équipe de soins, sans prise en compte de la chronologie : hospitalisation avec décompensation, hospitalisation sans décompensation, hospitalisation de jour (HDJ), consultation médicale, consultation par l’infirmière de pratique avancée (IPA), éducation thérapeutique (ETP) en externe, téléconsultation. La similarité des suivis est mesurée par la méthode LCS puis une classification ascendante hiérarchique (CAH) est réalisée pour identifier des typologies de suivi. Résultats L’analyse porte sur le suivi de 436 patients ayant eu 1 à 26 contacts avec l’équipe de soins. Pour 334 patients (77%), le suivi comprend au moins 4 contacts avec l’équipe. La CAH distingue 4 typologies de suivis dont les plus représentés (suivi modal) sont les suivants : type 1 avec 3 consultations IPA et 1 consultation médicale (N=63), type 2 avec 2 consultations médicales et 1 HDJ (N=93), type 3 avec au moins 3 consultations médicales (N=264) et type 4 avec de nombreux contacts avec l’équipe de soins dont des téléconsultations (N=16). Le type 1 comprend des adolescents plus âgés avec une moyenne de l’hémoglobine glyquée plus élevée et correspond aux patients en transition. Le groupe 4 correspond à des patients sous pompe à insuline pour lesquels un système automatisé de délivrance d’insuline est mis en place. Discussion/Conclusion Les suivis sont hétérogènes et la majorité des patients ont au moins 4 contacts avec l’équipe de soins sur un an. L’équipe adapte le suivi au profil des patients en termes d’intervenants et de fréquence d’intervention.

OBJECTIVE:Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear. DESIGN AND METHODS:Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries. RESULTS:Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively. CONCLUSIONS:Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

ABSTRACT Objective Effects of obesity on brain health have been revealed in adults, including mental health effects and cognitive impairment. Regarding cognition, obesity‐related memory impairment has been specifically described. While this effect could have a major impact on learning abilities during adolescence, few studies have considered this critical period. Methods In this present study, a new fMRI memory task based on paired encoding of faces and backgrounds and subsequent face recognition was presented to male adolescents living with obesity (N = 11) and their lean counterparts (N = 15). Results Our study shows that adolescents living with obesity exhibited significantly lower face recognition memory performances (F(1,72) = 9.84, p = 0.002) than their lean counterparts coupled with altered functional cerebral activation patterns during the encoding and retrieval phases of the task. More specifically, during the encoding of the task, a hypoactivation of the right hippocampus and the parahippocampal gyrus was identified in adolescents living with obesity and during the retrieval a hyperactivation of the precuneus (Z > 2.3, cluster‐corrected p = 0.05). Conclusions These results suggest that obesity during adolescence is associated with neurocognitive impairment. Future studies should consider adolescence more carefully since this memory impairment could contribute to academic learning difficulties faced by adolescents living with obesity. Trial Registration CHUBX 2017/19; CPP number: 2017‐3A02533‐50

Context:Neonatal diabetes mellitus (NDM) is a rare condition usually related to an identifiable genetic cause. Sulfonylurea therapy can ensure metabolic control, obviating the need for insulin while also improving neurodevelopmental outcomes. An oral glyburide suspension (OGS; AMGLIDIA) designed for pediatric use was introduced recently to eliminate the drawbacks of using crushed tablets. Objective:To evaluate the long-term effectiveness and safety of the OGS for NDM. Design:Retrospective cohort study. Setting:Fifteen centers in France. Patients:Consecutive patients started on OGS for NDM in 2015 through 2024. Intervention:OGS therapy. Main outcome measures:Glycated hemoglobin (HbA1c) values during OGS therapy; growth; and serious adverse events. Results:Of 27 patients, 22 had KCNJ11 mutations, 4 had ABCC8 mutations, and 1 had a 6q24 anomaly. Median follow-up during OGS therapy was 2.7 years (range, 2 months-9 years). At baseline, median HbA1c was 6.5% (5.8-7.9) overall and 6.5%, 6.4%, and 8.9% in the KCNJ11, ABCC8, and 6q24 subgroups, respectively. The median starting glyburide dose was 0.15 mg/kg/day (range, 0.1-0.185). HbA1c decreased nonsignificantly over time in all subgroups (P = .382), prompting in a small OGS dosage decrease. The last recorded HbA1c value was 6.3%, 5.9%, and 7.4% in the KCNJ11, ABCC8, and 6q24 subgroups, respectively. Serious adverse events were rare, with hypoglycemia in 2 patients during periods of decreased food intake and diarrhea in 1 patient. Conclusion:The OGS was effective in maintaining excellent metabolic control in the long term. The safety profile was good. The OGS should be considered for the first-line treatment of NDM.

Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.

CONTEXT:Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and is chiefly caused by thyroid dysgenesis (CHTD). The inheritance mode of the disease remains complex. OBJECTIVE:Gain insight into the inheritance mode of CHTD. METHODS:Prospective multicenter nationwide translational study in France including 514 patients with CH diagnosed through systematic newborn screening (HYPOTYGEN cohort). We focused on CHTD cases and studied their clinical and molecular phenotypes. Targeted next-generation sequencing using a 78-gene panel, including genes involved in thyroid development, function, transport, metabolism and action of thyroid hormones. Statistical analysis, familial segregation, and in vitro functional studies focusing on cell migration have been performed. RESULTS:We analyzed the clinical phenotypes of 458 patients with CH. Cardiac and renal malformations were present in 7.7% (14/182) and 3.9% (7/178) of patients, respectively. Genetic analysis was performed on 292 patients of the cohort, based on criteria for ethnicity and availability of DNA samples for index cases and their parents. A disease-causing mutation in 1 of the 10 known genes for CHTD was identified in 20/292 (6.8%) patients. We found a digenic mode of inheritance in 16 (5.5%) patients, each carrying a variant in a thyroid development gene and a variant in the H2O2 generation complex gene DUOX2/DUOXA2. Familial segregation analysis and in vitro functional studies supported this model. CONCLUSION:This work expands our understanding of the molecular causes of CHTD by demonstrating that digenic inheritance can be implicated, with deleterious variants in thyroid development and DUOX2/DUOXA2 genes. The complexity of this model implies a revision of the genetic landscape of CHTD and specific clinical care of patients during long-term follow-up.

BACKGROUND:During the perinatal period several maternal and obstetric risk factors are known to be associated with overweight and childhood obesity. METHOD:The aim of this study was to determine the prevalence of risk factors for childhood obesity identifiable at birth. Data extracted from the computerized medical record (DXCARER) women who gave birth in the maternity ward of the University hospital of Bordeaux during a 11 months-period constituted an anonymized database to calculate the prevalence of the following risk factors: maternal obesity prior to pregnancy, excessive weight gain during pregnancy, maternal smoking, gestational diabetes, low socioeconomic status, cesarean delivery, macrosomia, and lack of breastfeeding. After eliminating duplicates and women for whom data on risk factors were missing, the population available for analysis was 1977 women who responded to inclusion criteria. RESULTS:At the onset of pregnancy, mean age of women was 31.6 years [± 5.2] and mean BMI was 23.9 kg / m² [± 4.9], a third of them being overweight or obese. During pregnancy, half of women had excessive weight gain, gestational diabetes occurred in 15.9 % of them, 15.9 % smoked, and 18.1 % were in a precarious situation. Children were born by cesarean section in 15.3 % of cases. Depending on the definition used, exact birth weight (BW) or Audipog formula (percentile), neonates were large for gestational age in respectively 6.7 % of cases (BW> 4000 g) or 11 % (> 90th percentile) and small for gestational age in respectively 3 % of cases (BW <2500 g) and 6.8 % (<10th percentile). They were formula fed in 28.7 % of cases. The multivariate analysis showed that the association between excessive weight gain during pregnancy and birth weight is influenced by all other risk factors, except breastfeeding. CONCLUSION:Risk factors for developing childhood obesity, which are largely interrelated and influenced by medical care, can be identified as early as the maternity ward. Based on their prevalence, the development of a risk score will make it possible to set up an intervention program for the early prevention of childhood obesity right from the maternity ward.

Le surpoids et l’obésité sont devenus un enjeu de Santé publique en raison des nombreuses complications associées qui engendrent une morbidité et un coût majeur pour la société. Le risque de rester obèse à l’âge adulte concerne environ la moitié des enfants obèses, augmentant fortement si l’obésité persiste à l’adolescence. La période des « 1000 premiers jours », allant de la conception aux 2 ans de l’enfant, est une période charnière pour le risque métabolique à long terme. Pendant cette période de vulnérabilité, plusieurs facteurs de risque maternels et obstétricaux ont été montrés comme étant associés au surpoids et à l’obésité infantile. Le repérage précoce des enfants à risque de développer une obésité devrait permettre des actions de prévention, basées sur l’accompagnement des familles dans la mise en place de comportements favorables à la santé dès le plus jeune âge.

BACKGROUND:The number of patients with type 2 diabetes (T2D) and type 1 diabetes (T1D) is on the rise, partly due to a global increase in new T1D cases among children. Beyond the well-documented microvascular and macrovascular complications, there is now substantial evidence indicating that diabetes also impacts the brain, leading to neuropsychological impairments. The risk of developing neuropsychiatric symptoms is notably higher in childhood due to the ongoing maturation of the brain, which makes it more susceptible to damage. Despite this awareness, the specific effects of diabetes on cognitive function remain poorly understood. SUMMARY:This review synthesizes literature on the impact of diabetes on cognition and its relationship with brain structural changes. It presents data and hypotheses to explain how T1D contributes to cognitive dysfunction, with a particular focus on children and adolescents. The emphasis on the pediatric population is intentional, as young diabetic patients typically have fewer comorbidities, reducing confounding factors and simplifying the investigation of cognitive alterations. KEY MESSAGE:We examine the roles of hypo- and hyperglycemia, as well as the emerging role of glucocorticoids in the development of neuropsychological disorders. When specific mechanisms related to T1D are available, they are highlighted; otherwise, data and hypotheses applicable to both T1D and T2D are discussed.

Background. Poor glycemic control in patients with type 1 diabetes (T1D) is associated with greater social deprivation. However, the evidence is inconsistent in terms of the type of social deprivation (individual-level or area-level) and whether glycemic control changes over time. Here, we investigated the impacts of individual-level and area-level social deprivation on the glycated hemoglobin (HbA1c) trajectory from the time of T1D diagnosis. Materials and Methods. We retrospectively analyzed a cohort of children who were diagnosed with T1D between 2017 and 2020 at Bordeaux University Hospital. Social deprivation was assessed using both parental individual indicator (EPICES score) and ecological indicator (European Deprivation Index (EDI) score). Piecewise linear mixed-effects models were used to estimate the effects of social deprivation on HbA1c trajectory. Results. We included 168 patients. The most-deprived group included 29% and 22% of all patients, as revealed by the respective EPICES and EDI scores. The two indicators were poorly correlated. The short-term decrease in HbA1c level tended to be smaller in the most-deprived patients over the first 4 months after diagnosis than in other patients (slope difference of 2.68% per year compared with the slope among the least-deprived patients, P=0.056). The long-term trajectory was influenced by area-level deprivation (EDI score); the least-deprived patients (quintile 1) exhibited more stable mean HbA1c levels. Conclusions. Social deprivation may partially explain poor glycemic control in some patients; both short-term individual deprivation and long-term area-level deprivation may be involved. Further research is needed to determine how to integrate this information into a therapeutic strategy.

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disorder involving isolated aldosterone deficiency without any compromise of other adrenal hormones. This condition manifests mainly in the neonatal period and in infants as a salt wasting syndrome with vomiting and failure to thrive. Due to its potentially life-threatening effects, ASD requires a careful and early diagnosis based on appropriate hormonal investigations in order to initiate adequate management: rehydration as well as salt and fludrocortisone supplementation. Genetic analysis of the CYP11B2 gene will confirm ASD in most cases. We report the case of a newborn with a typical clinical presentation associated with some uncommon phenotypic features (hyperhidrosis, liver injury). Furthermore, our patient carries a new CYP11B2 splicing variant to be added to the approximately 60 pathogenic or likely pathogenic variants already reported.

Hypopituitarism (or pituitary deficiency) is a rare disease with an estimated prevalence of between 1/16,000 and 1/26,000 individuals, defined by insufficient production of one or several anterior pituitary hormones (growth hormone [GH], thyroid -stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], luteinizing hormone [LH], follicle -stimulating hormone [FSH], prolactin), in association or not with diabetes insipidus (antidiuretic hormone [ADH] deficiency). While in adults hypopituitarism is mostly an acquired disease (tumors, irradiation), in children it is most often a congenital condition, due to abnormal pituitary development. Clinical symptoms vary considerably from isolated to combined deficiencies and between syndromic and non-syndromic forms. Early signs are non-specific but should not be overlooked. Diagnosis is based on a combination of clinical, laboratory (testing of all hormonal axes), imaging (brain magnetic resonance imaging [MRI] with thin slices centered on the hypothalamic -pituitary region), and genetic (next -generation sequencing of genes involved in pituitary development, array -based comparative genomic hybridization, and/or genomic analysis) findings. Early brain MRI is crucial in neonates or in cases of severe hormone deficiency for differential diagnosis and to inform syndrome workup. This article presents recommendations for hormone replacement therapy for each of the respective deficient axes. Lifelong follow-up with an endocrinologist is required, including in adulthood, with multidisciplinary management for patients with syndromic forms or comorbidities. Treatment objectives include alleviating symptoms, preventing comorbidities and acute complications, and optimal social and educational integration. (c) 2024 The Authors. Published by Elsevier Masson SAS on behalf of French Society of Pediatrics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)