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Age at diagnosis (AAD) of Type 1 diabetes (T1D) is determined by the age at onset of the autoimmune attack and by the rate of beta cell destruction that follows. Twin studies found that T1D AAD is strongly influenced by genetics, notably in young children. In young UK, Finnish, Sardinian patients AAD-associated genomic variants were previously identified, which may vary across populations and with time. In 1956 children of European ancestry born in mainland France in 1980-2008 who declared T1D before 15 years, we tested 94 T1D-associated SNPs for their association with AAD using nonparametric Kruskal-Wallis test. While high-risk HLA genotypes were not found to be associated with AAD, fourteen SNPs located in 12 non-HLA loci showed a strong association (2.9 × 10-12 < P < 1.4 × 10-3 after FDR correction). Four of these loci have been associated with AAD in previous cohorts (GSDMB, IL2, TNFAIP3, IL1), supporting a partially shared genetic influence on AAD of T1D in the studied European populations. In contrast, the association of 8 new loci CLEC16A, TYK2, ERBB3, CCR7, FCRL3, DNAH2, FGF3/4, and HPSE2 with AAD is novel. The 12 protein-coding genes located within these loci are involved in major immune pathways or in predisposition to other autoimmune diseases, which suggests a prominent role for these genes in the early immune mechanisms of beta cell destruction.
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SOFT syndrome (Short stature-Onychodysplasia-Facial dysmorphism-hypoTrichosis) is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A encoding a centriolar protein. To refine the phenotypic spectrum of SOFT syndrome, recently shown to include metabolic features, we conducted a systematic review of all published cases (19 studies, including 42 patients). The SOFT tetrad affected only 24 patients (57%), while all cases presented with short stature from birth (median height: -5.5SDS([-8.5]-[-2.8])/adult height: 132.5 cm(103.5-148)), which was most often disproportionate (90.5%), with relative macrocephaly. Bone involvement resulted in short hands and feet (100%), brachydactyly (92.5%), metaphyseal (92%) or epiphyseal (84%) anomalies, and/or sacrum/pelvis hypoplasia (58%). Serum IGF-I was increased (median IGF-I level: + 2 SDS ([-0.5]-[+ 3])). Recombinant human growth hormone (rhGH) therapy was stopped for absence/poor growth response (7/9 patients, 78%) and/or hyperglycemia (4/9 patients, 45%). Among 11 patients evaluated, 10 (91%) presented with central distribution of fat (73%), clinical (64%) and/or biological insulin resistance (IR) (100%, median HOMA-IR: 18), dyslipidemia (80%), and hepatic steatosis (100%). Glucose tolerance abnormalities affected 58% of patients aged over 10 years. Patients harbored biallelic missense (52.4%) or truncating (45.2%) POC1A variants. Biallelic null variants, affecting 36% of patients, were less frequently associated with the SOFT tetrad (33% vs 70% respectively, p = 0.027) as compared to other variants, without difference in the prevalence of metabolic abnormalities. POC1A should be sequenced in children with short stature, altered glucose/insulin homeostasis and/or centripetal fat distribution. In patients with SOFT syndrome, rhGH treatment is not indicated, and IR-related complications should be regularly screened and monitored.PROSPERO registration: CRD42023460876.
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OBJECTIVE: This study aimed to describe the clinical, biochemical, therapeutic, and progressive characteristics of children with familial type 1 diabetes (T1D) compared to those with non-familial T1D. Compare within the first group, the phenotype of type 1 diabetics inherited from the father with those inherited from the mother. PATIENTS AND METHODS: We conducted a retrospective study lasting 10 years at the L'hôpital Femme Mère Enfant (Woman-Mother-Child Hospital) in Lyon, France. Cases were any child diagnosed with T1D for at least 12 months who had a parent with T1D. Each case was matched with a T1D control without a family history of T1D, of the same age, same sex and same year of discovery. Cases group was divided into two subgroups according to the sex of the parent with T1D. RESULTS: A total of 43 children had a TD1 parent (family group) of whom 27 cases were the father. Forty four T1D children without any T1D parent were matched (sporadic group). The family group had consulted earlier (p < 0.001), were less in initial diabetic ketoacidosis (p = 0.016), and had a lower HbA1C level lower (p < 0.001) and lower initial insulin requirements (p < 0.001). During follow-up, it was noted that the evolution of Hb1AC, insulin requirements, and chronic complications were similar in familial and non-familial cases (p = 0.943, p = 0.450, p = 0.664, respectively). The patients in the T1D mother group seemed better balanced than those of the T1D father with an average HbA1C at 10 years of follow-up of 7.82% in the maternal group compared to 9.10% in the paternal group (p = 0.021). CONCLUSION: This study shows that familial T1D is a protective factor against the initial severity of T1D in offspring. Paternal T1D presents a more severe initial and progressive clinico-biological character than T1D inherited from the mother. However, during follow-up, other psycho-environmental factors could modify this observation.
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INTRODUCTION: Disturbances in plasma sodium levels are a major complication following recent resections of craniopharyngiomas in children. They must be properly managed to avoid neurological sequelae. We aimed to describe the variations and characteristics of postoperative natremia in children who had undergone a first craniopharyngioma resection with a particular focus on the frequency of triphasic syndrome in these patients. METHODS: Paediatric patients with craniopharyngiomas who underwent a first surgical resection in the neurosurgery department of the Hôpital Femme Mère Enfant (Lyon, France) between January 2010 and September 2021 were included in the present study and the medical records were analysed retrospectively. RESULTS: A total of 26 patients were included. Of these, 17 (65.4%) had a postoperative course characterised by the occurrence of both initial diabetes insipidus (DI) and hyponatremia a few days later. Eight patients (30.8%) presented then with isolated and persistent DI. Patients with the triphasic syndrome had a significantly higher grade of Puget classification on MRI (1 and 2), compared to the other patients. CONCLUSION: Dysnatremia is common after craniopharyngioma resections in children. This immediate postoperative complication is particularly difficult to manage and requires rapid diagnosis and prompt initiation of medical treatment to minimize fluctuations in sodium levels and avoid neurological sequelae.
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Craneofaringioma , Neoplasias Hipofisarias , Complicaciones Posoperatorias , Sodio , Humanos , Craneofaringioma/cirugía , Craneofaringioma/sangre , Femenino , Masculino , Niño , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/sangre , Sodio/sangre , Francia/epidemiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Adolescente , Preescolar , Estudios Retrospectivos , Estudios de Cohortes , Hiponatremia/etiología , Hiponatremia/sangre , Procedimientos Neuroquirúrgicos/efectos adversos , Diabetes Insípida/etiología , Diabetes Insípida/sangre , Diabetes Insípida/epidemiologíaRESUMEN
STUDY QUESTION: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER: This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY: Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION: This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE: The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS: The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: In-house #23-5214 registered study.
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Hormona Folículo Estimulante , Hormona Luteinizante , Pubertad Precoz , Humanos , Femenino , Pubertad Precoz/orina , Pubertad Precoz/diagnóstico , Pubertad Precoz/sangre , Estudios Retrospectivos , Niño , Hormona Luteinizante/sangre , Hormona Luteinizante/orina , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/orina , Inmunoensayo/métodos , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: SOFT syndrome (MIM#614813), denoting Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis, is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A, encoding a centriolar protein. SOFT syndrome, characterized by severe growth failure of prenatal onset and dysmorphic features, was recently associated with insulin resistance. This study aims to further explore its endocrinological features and pathophysiological mechanisms. DESIGN/METHODS: We present clinical, biochemical, and genetic features of 2 unrelated patients carrying biallelic pathogenic POC1A variants. Cellular models of the disease were generated using patients' fibroblasts and POC1A-deleted human adipose stem cells. RESULTS: Both patients present with clinical features of SOFT syndrome, along with hyperinsulinemia, diabetes or glucose intolerance, hypertriglyceridemia, liver steatosis, and central fat distribution. They also display resistance to the effects of IGF-1. Cellular studies show that the lack of POC1A protein expression impairs ciliogenesis and adipocyte differentiation, induces cellular senescence, and leads to resistance to insulin and IGF-1. An altered subcellular localization of insulin receptors and, to a lesser extent, IGF1 receptors could also contribute to resistance to insulin and IGF1. CONCLUSIONS: Severe growth retardation, IGF-1 resistance, and centripetal fat repartition associated with insulin resistance-related metabolic abnormalities should be considered as typical features of SOFT syndrome caused by biallelic POC1A null variants. Adipocyte dysfunction and cellular senescence likely contribute to the metabolic consequences of POC1A deficiency. SOFT syndrome should be included within the group of monogenic ciliopathies with metabolic and adipose tissue involvement, which already encompasses Bardet-Biedl and Alström syndromes.
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Anomalías Múltiples , Ciliopatías , Resistencia a la Insulina , Insulinas , Humanos , Proteínas de Ciclo Celular/genética , Proteínas del Citoesqueleto/genética , Factor I del Crecimiento Similar a la Insulina , Resistencia a la Insulina/genética , Ciliopatías/genética , Anomalías Múltiples/genéticaRESUMEN
AIM: To investigate glycaemic outcomes in youths and adults with type 1 diabetes with either MiniMed™ 780G or Tandem t:slim X2™ control-IQ automated insulin delivery (AID) systems and to evaluate clinical factors that migrate, mitigate the achievement of therapeutic goals. MATERIALS AND METHODS: This retrospective, real-world, observational study was conducted in a specialized university type 1 diabetes centre with patients observed for 3-12 months post-initiation of an AID system. Primary outcomes were the percentage time in the target glucose range [TIR70-180 mg/dl (3.9-10 mmol/L)] as measured by continuous glucose monitoring, mean glucose management indicator (GMI) and glycated haemoglobin (HbA1c) levels. RESULTS: Our study cohort consisted of 48 adolescents and 183 adults (55% females) aged 10-77 years. The mean (95% confidence interval) TIR70-180 mg/dl after 30 days was higher than baseline and by 14% points after 360 days with 71.33% (69.4-73.2) (n = 123, p < .001). HbA1c levels decreased by 0.7% and GMI by 0.6% after 360 days. The proportion of time spent <70 mg/dl (3.9 mmol/L) was not significantly different from baseline. During follow-up, 780G users had better continuous glucose monitoring results than control-IQ users but similar HbA1c levels, and an increased risk of weight gain. Age at onset influenced TIR70-180 mg/dl in univariate analysis but there was no significant relationship after adjusting on explanatory variables. Baseline body mass index did not influence the performance of AID systems. CONCLUSIONS: This analysis showed the beneficial effects of two AID systems for people with type 1 diabetes across a broad spectrum of participant characteristics. Only half of the participants achieved international recommendations for glucose control with TIR70-180 mg/dl >70%, HbA1c levels or GMI <7%, which outlines the need to maintain strong educational and individual strategies.
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Diabetes Mellitus Tipo 1 , Insulina , Adulto , Femenino , Humanos , Adolescente , Masculino , Insulina/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada , Automonitorización de la Glucosa Sanguínea/métodos , Estudios Retrospectivos , Estudios de Seguimiento , Glucemia/análisis , Insulina Regular Humana/uso terapéutico , Glucosa/uso terapéutico , Sistemas de Infusión de InsulinaRESUMEN
INTRODUCTION: The management of childhood type 1 diabetes requires the active participation of parents. The aim of the present study was to describe the main characteristics of parents of children with type 1 diabetes, including objective burden regarding time spent on diabetes care, emotional distress (exhaustion, need for respite, quality of life), and symptoms of depression as well as anxiety. METHODS: In this observational study, parents of children with type 1 diabetes completed a questionnaire, anonymously. Different questions were asked to the parent about the objective burden of diabetes and its repercussion, their exhaustion and need for respite. Two validated instruments (HADS, WHOQOL-BREF) have been integrated into the questionnaire. RESULTS: Eighty eight parents were included in the study. Among them, 76 (86%) were mothers. All the parents with a child aged 6 years or younger (10/10) reported having to take care of their child's diabetes twice or more a day, this was the case for 37/39 (94.9%) parents of children aged 7 to 13, and for 16/36 (44.4%) of parents of children aged 14 years or above. In the total population, 33/86 (38.4%) parents declared getting up every night because of their child's diabetes. The median daily time spent on diabetes management was 40 minutes. There were 54 parents (62.8%) who reported moderate-strong exhaustion, and 27 (30.7%) who expressed a moderate-strong need for respite. Regarding the result of the HADS, 46 parents (55.4%) reported symptoms of anxiety and/or depression. DISCUSSION/CONCLUSION: Parents of children with type 1 diabetes must carry out multiple daily care, at all times of day and night. Their emotional state can be impacted with, in particular, a risk of exhaustion. Screening for these difficulties should be a part of the overall management of a child with type 1 diabetes and his family to limit various complications.
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Monogenic obesity generally results in severe early-onset obesity associated with abnormal feeding behavior and endocrine disorders. We report here an extremely severe case of early-onset obesity associated with hyperphagia in an 11-month-old boy without other signs of a syndromic obesity. He developed severe obstructive sleep apnea, dyslipidemia, hepatic steatosis with cytolysis, and acanthosis nigricans with insulin resistance in the first months of life. Laboratory investigations showed an elevated serum leptin level (80.03 ng/mL, normal range 2.45-6.55 ng/mL). Next-generation sequencing of obesity genes panel identified a novel homozygous intronic variant in leptin receptor gene (LEPR), c.703 + 5G>A, predicting affected splicing that resulted in a frameshift, premature stop, and truncation of the protein beyond the cytokine receptor homology domain 1. The child died at 27 months of age in the absence of available specific drug therapy.
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Obesidad , Receptores de Leptina , Masculino , Humanos , Preescolar , Lactante , Receptores de Leptina/genética , Obesidad/complicaciones , Obesidad/genética , Muerte , Conducta Alimentaria , Mutación del Sistema de LecturaRESUMEN
The increase in life expectancy of patients with cystic fibrosis has come with new comorbidities, particularly diabetes. The gradual development of glucose tolerance abnormalities means that 30 to 40% of adults will be diabetic. Cystic fibrosis-related diabetes is a major challenge in the care of these patients because it is a morbidity and mortality factor at all stages of the disease. Early glucose tolerance abnormalities observed from childhood, before the stage of diabetes, are also associated with a poor pulmonary and nutritional outcome. The long asymptomatic period justifies systematic screening with an annual oral glucose tolerance test from the age of 10 years. However, this strategy does not take into account the new clinical profiles of patients with cystic fibrosis, recent pathophysiological knowledge of glucose tolerance abnormalities, and the emergence of new diagnostic tools in diabetology. In this paper, we summarise the challenges of screening in the current context of new patient profiles - patients who are pregnant, have transplants, or are being treated with fibrosis conductance transmembrane regulator modulators - and put forward an inventory of the various screening methods for cystic fibrosis-related diabetes, including their applications, limitations and practical implications.
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Fibrosis Quística , Diabetes Mellitus , Intolerancia a la Glucosa , Adulto , Humanos , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Prueba de Tolerancia a la Glucosa , Comorbilidad , Glucosa , Glucemia , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/epidemiologíaRESUMEN
STUDY OBJECTIVES: Narcolepsy with cataplexy is associated with obesity in children. We proposed to assess whether metabolic complications were linked to narcolepsy regardless of obesity. The second aim of the study was to compare endocrine comorbidities in obese children with narcolepsy and control patients. METHODS: We performed a case-control study in Pediatric Sleep Unit and Pediatric Endocrinology Unit of Woman Mother Child Hospital (Lyon, France) comparing 22 children with narcolepsy with 22 sex-, pubertal stage-, and BMI-matched non-syndromic obese patients. Clinical examination, biological measurements including an oral glucose tolerance test, and abdominal ultrasound were performed. RESULTS: No difference regarding glucidic, lipid profile, hepatic, respiratory, and cardiovascular parameters were found between narcoleptic and control participants. Insulin sensitivity did not differ between the two groups. Control patients had more first-degree family history of overweight or obesity than children with narcolepsy (83% vs. 50%, p = .05). Prevalence of precocious puberty in children with narcolepsy was not higher than in control participants, but all the cases of advanced puberty involved children with narcolepsy who were diagnosed before 11 years old. All cases of central hypothyroidism belong to the narcoleptic group, who presented lower thyroid-stimulating hormone and fTA values compared to control children (respectively p = .03 and p = .001). CONCLUSIONS: No difference regarding metabolic complications was found between children with narcolepsy and control participants. Thus, metabolic disorders may be related to weight gain rather than a narcolepsy-specific risk. The presence of hypothyroidism and advanced puberty suggests a global involvement of hypothalamic structures in children with narcolepsy.
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Cataplejía , Narcolepsia , Obesidad Infantil , Femenino , Humanos , Niño , Obesidad Infantil/complicaciones , Obesidad Infantil/epidemiología , Estudios de Casos y Controles , Narcolepsia/complicaciones , Narcolepsia/epidemiología , Narcolepsia/diagnóstico , Cataplejía/complicaciones , Cataplejía/epidemiología , ComorbilidadRESUMEN
Maturity-Onset Diabetes of the Youth (MODY) diabetes remains commonly misdiagnosed. A monogenic form should be suspected in individuals presenting hyperinsulinemic hypoglycemia (HH) associated with, either later development of MODY (hypoglycemia-remission-diabetes sequence), or with first/second-degree family history of diabetes. Herein, we aimed to describe this individual or family monogenic association between HH and diabetes, and identify potential genotype-phenotype correlations. We conducted a systematic review of 26 studies, including a total of 67 patients with this association resulting from variants in GCK (n = 5 cases), ABCC8 (n = 29), HNF1A (n = 5), or HNF4A (n = 28). A family history of hypoglycemia and/or diabetes was present in 91% of cases (61/67). Median age at first hypoglycemia was 24 h after birth. Diazoxide was initiated in 46 children (46/67-69%); responsiveness was found in 91% (42/46). Median HH duration was three years (1 day-25 years). Twenty-three patients (23/67-34%) later developed diabetes (median age: 13 years; range: 8-48); more frequently in those untreated with diazoxide. This association was most commonly inherited in an autosomal dominant manner (43/48-90%). Some genes were associated with less severe initial hypoglycemia (HNF1A), shorter duration of HH (HNF4A), and more maternal (ABCC8) or paternal (HNF4A) transmission. This study illustrates that the same genotype can give a biphasic phenotype in the same person or a reverse phenotype in the same family. Wider awareness of this association is necessary in pediatrics to establish annual monitoring of patients who have presented HH, and during maternity to screen diabetes and optimize genetic counseling and management of pregnancy, childbirth, and the newborn.PROSPERO registration: CRD42020178265.
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Hiperinsulinismo Congénito , Diabetes Mellitus Tipo 2 , Niño , Hiperinsulinismo Congénito/genética , Diabetes Mellitus Tipo 2/genética , Diazóxido/uso terapéutico , Femenino , Humanos , Mutación , Fenotipo , EmbarazoRESUMEN
OBJECTIVES: Serious hyperinsulinemic hypoglycemia (HH) is generally the main initial symptom of hyperinsulinism. Epilepsy, without any overt feature of hypoglycemia, might be a very rare initial presentation of late-onset isolated hyperinsulinism. CASE PRESENTATION: We describe a case of late-onset HH in a 15-year-old boy with a history of idiopathic generalized epilepsy, now named genetic generalized epilepsy (IGE/GGE), beginning with a tonic-clonic seizure at the age of 11 years. Subsequently, absences with rare eyelid myoclonia were recorded on electroencephalogram (EEG), followed by episodes of impaired consciousness with facial myoclonia. Neurological status was normal except attention-deficit hyperactivity disorder (ADHD). At the age of 15 years, an episode of slight alteration of consciousness with neurovegetative signs could be recorded, which did not correspond to an absence status. Hypoglycemia due to hyperinsulinism was documented (clinically, biologically, and genetically). Diazoxide treatment resolved the glycopenic symptoms, the non-hypoglycemic seizures and normalized brain electrical activity allowing complete withdrawal of antiepileptic medication. CONCLUSIONS: Epilepsy can be a very rare initial feature of HH starting in childhood. The occurrence of atypical features in the context of GGE as "absence statuses" with unusual vegetative symptoms and facial myoclonia might be suggestive for HH. Careful assessment and specific treatment are necessary to prevent hyperinsulinism related brain damage. Our case showed that diazoxide might also resolve seizures and normalize EEG.
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Antihipertensivos/uso terapéutico , Hiperinsulinismo Congénito/complicaciones , Diazóxido/uso terapéutico , Epilepsia Generalizada/tratamiento farmacológico , Adolescente , Epilepsia Generalizada/etiología , Epilepsia Generalizada/patología , Humanos , Masculino , PronósticoRESUMEN
BACKGROUND: Due to the low resolution of historical imaging technologies, descriptions of Septic Arthritis of Facet Joint (SAFJ) in children are scarce, though severe cases are known. We first aimed to estimate the incidence rate of SAFJ in children; we further aimed to specify SAFJ clinical, imaging and laboratory findings, and identify avenues for appropriate management. METHODS: A 10-year consecutive SAFJ case series using our imaging center database combined with a 50-year systematic review of literature cases. RESULTS: The mean ± SD incidence of pediatric SAFJ was 0.23 ± 0.4/100,000 children-years. The key symptoms were potty refusal (in toddlers) or painful sitting (78%) and lateralized signs (paravertebral tenderness and/or swelling, 88%). SAFJ diagnosis and extension were obtained using magnetic resonance imaging (MRI) (94%), and found an epidural extension in 8/16 cases. The mean duration of antibiotic treatment was 5.1 weeks. The compliance with guidelines was 79% for empiric and 62% for targeted antibiotic therapies. CONCLUSIONS: SAFJ incidence in children is much greater than expected from the literature. Half of cases were complicated by an epidural infection. Simple clinical symptoms detected as early as the bedside allow a strong suspicion of SAFJ, justifying the use of a first-line MRI to confirm the diagnosis and precisely describe the extension. Focusing on simple clinical signs is key to justify the transfer of a child or the shortening of the delay to obtain an MRI. However, as MRI availability increases in most Western countries, and the capacity for diagnosis increases, the awareness of SAFJ must be spread to avoid missed cases.
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Artritis Infecciosa/diagnóstico por imagen , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/epidemiología , Articulación Cigapofisaria , Adolescente , Antibacterianos/uso terapéutico , Artritis Infecciosa/terapia , Niño , Preescolar , Bases de Datos Factuales , Femenino , Francia/epidemiología , Humanos , Incidencia , Lactante , Imagen por Resonancia Magnética , Masculino , Evaluación de SíntomasRESUMEN
Donohue syndrome (leprechaunism; OMIM *246200) is a rare and often lethal autosomal recessive disease caused by mutations in the INSR gene. We report the case of a 29-year-old pregnant woman, primigravida, who was referred at 33 weeks of gestation for severe intrauterine growth restriction (IUGR). Ultrasound examination found severe IUGR associated with an obstructive hypertrophic cardiomyopathy (HCM), confirmed postnatally. The newborn's blood glucose level fluctuated from fasting hypoglycemia to postprandial hyperglycemia. The infant was found to be homozygous for a novel missense pathogenic variant, c.632C>T (p.T211l), in exon 2 of the INSR gene, predicted to result in an abnormal insulin receptor. To our knowledge, this is the first report of leprechaunism being revealed by IUGR and HCM during the prenatal period. Clinicians should keep in mind that the association of these prenatal signs could indicate leprechaunism and specific early neonatal management could be proposed, in particular with recombinant human insulin-like growth factor-I.