Hémochromatose périnatale (comment réaliser le diagnostic)

L hémochromatose périnatale (HP) est une pathologie rare, définie par l association d une atteinte hépatique et d une surcharge en fer hépatique et extra hépatique épargnant le système réticulo-endothélial. Le diagnostic est difficile à faire. Sa physiopathologie reste imparfaitement connue et plusieurs pathologies peuvent présenter ce phénotype. L hypothèse actuelle repose sur un mécanisme allo-immun. Un traitement immunomodulateur a été essayé, avec succès, chez des femmes ayant eu des grossesses compliquées d HP d étiologie allo-immune possible. Ce traitement présente des effets secondaires, les femmes pouvant en bénéficier doivent donc être sélectionnées avec rigueur. Devant l enjeu de ce traitement, un diagnostic de certitude devient nécessaire. Depuis 2006, un comité d experts a été créé en France pour étudier les dossiers suspects d HP et statuer sur le degré de certitude d un mécanisme immun possible afin de valider l indication d un traitement immunomodulateur chez ces femmes. Ce travail reprend et analyse les résultats de l expertise de 54 dossiers. Nous rapportons la plus grande série de cas d HP d origine allo-immune possible. Nous confirmons l absence de spécificité de critères cliniques ou biologiques dans cette pathologie et insistons sur la nécessité d une étude histologique complète pour confirmer ce phénotype. Nous proposons un arbre diagnostique ayant pour but d aider le praticien non spécialiste dans sa pratique. Dans l attente de la mise en évidence d une cible antigénique, et devant la complexité de ce diagnostic le recours à un comité d expert reste indispensable pour valider l indication d un traitement immunomodulateur préventif.LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A pilot Study to develop a tool for the assesment of osteopathic student’s clinical reasoning

Introduction: At a time when osteopathy is moving towards evidence-based practice, it is becoming necessary to implement teaching methods and practices that are themselves evidence-based. There are studies on clinical reasoning in osteopathic education, and broadly in medical education, but to date none have really led to an assessment tool for clinical practice. In France, new decrees impose competency based curricula on academic institutions, forcing them to redefine new reliable assessment tools. The aim of the present study is to develop a clinical tool to assess the clinical reasoning of osteopathic student. Methods: At CEESO Paris, we reviewed our existing tool used for the clinical assessment of students. Each item of the assessment tool was subject to a double comparison with the literature on clinical reasoning and the competencies defined by the decrees, leading to a criterion referenced tool allowing to identify the students clinical reasoning difficulties. Clinical supervisors were recruited to test this tool during the supervision of students at the CEESO Paris osteopathic clinic and to offer their feedback on this new tool during individual interview (qualitative analysis). Content validity and convergent validity of the tool were also be analyzed using questionnaire (quantitative analysis). Participants were also asked to indicate the expected achievement period for each criterion. Results: 7 clinical supervisors volunteered. Based on quantitative analysis, the assessment tool showed good docimological qualities, except for Predictive validity. There were large discrepancies in responses regarding the expected period of success for each criterion. The qualitative analysis showed that supervisors considered the grid to be a good tool for formative assessment of clinical reasoning. It facilitated a dialogue on the difficulties encountered by the students and on the student's competencies. Conclusion: the tool seems to be promising for the assessment of the clinical reasoning of osteopathic students. Further research is needed to assess the reliability of the tool and its relevance for the summative evaluation. It is also necessary to identify difficulties encountered by users that could bias the assessment or the monitoring of student’ progress

An unusual cause of abdominal obstruction in a 10-year-old boy successfully treated by endoscopy.

International audienceNo abstract availabl

Evaluation of the accuracy of exchangeable copper and relative exchangeable copper (REC) in a mouse model of Wilson's disease.

International audienceWilson's disease (WD) is caused by mutations in the ATP7B gene responsible for a toxic copper overload mainly in the liver and the central nervous system. Phenotypic heterogeneity may challenge the diagnostic confirmation. Exchangeable copper (CuEXC) has recently been proposed as a new marker of WD, and its ratio to the total serum copper (Cus), Relative Exchangeable Copper (REC = CuEXC/Cus), as a diagnostic marker. This study aimed to investigate whether this could be confirmed in Atp7b-/- mice, an engineered WD animal model. Atp7b-/- (n = 137) and wild type (WT; n = 101) mice were investigated under the same conditions at 6-8, 20, 39, or 50 weeks of age. Twenty-four Atp7b-/- mice received D-penicillamine treatment from 39 to 50 weeks of age. Serum and liver [histology and intrahepatic copper (IHCu)] data were evaluated. In the WT group, all serum and liver data were normal. Atp7b-/- livers developed a chronic injury from isolated moderate inflammation (6-8 weeks: 16/33 = 48%) to inflammatory fibrosis with cirrhosis (50 weeks: 25/25 = 100% and 16/25 = 64% respectively). Cus and CuEXC increased until week 39, whereas IHCu and REC were stable with increasing age and much higher than in WT mice (mean ± SD: 669 ± 269 vs. 13 ± 3 μg/g dry liver and 39 ± 12 vs. 11 ± 3%, respectively). A threshold value of 20% for REC provided a diagnostic sensitivity and specificity of 100%, regardless of sex, age, or the use of D-penicillamine. Eleven weeks of 100 mg/kg D-penicillamine reduced liver fibrosis (p = 0.001), IHCu (p = 0.026) and CuEXC (p = 0.175). In conclusion, this study confirms REC as a WD diagnostic marker in a mouse model of chronic liver disease caused by copper overload. Further studies are needed to assess the usefulness of CuEXC to monitor the evolution of WD, particularly during treatment

Relative exchangeable copper: A valuable tool for the diagnosis of Wilson disease

International audienceBackground & Aims: Measuring of the relative exchangeable copper seems to be a promising tool for the diagnosis of Wilson disease. The aim of our study is to determine the performance of REC for the diagnosis of Wilson disease in a population of patients with chronic liver diseases. Methods: Measuring of exchangeable serum copper levels and relative exchangeable copper was performed in a group of Wilson disease patients at diagnosis or at clinical deterioration because of non-compliance (group 1, n=9), a group of stable WD patients (group 2, n=40), and two groups of patients (adult and paediatric) followed for non-Wilsonian liver diseases (group 3, n=103 and group 4, n=49 respectively). Results: Exchangeable serum copper (N: 0.6-1.1 mu mol/L) was significantly higher in group 1 (mean 2.2 +/- 0.7 mu mol/L) compared to the other three groups: group 2=0.9 +/- 0.4 mu mol/L, group 3=1.2 +/- 0.4 mu mol/L, group 4=1.1 +/- 0.3 mu mol/L (P\textless0.05). Relative exchangeable copper was significantly higher in Wilson disease patients group 1 and 2 (mean 52.6% and 43.8%) compared to patients suffering from other liver diseases (mean 7.1% and 5.9%) (P\textless0.05). Conclusions: Our study confirms that the determination of relative exchangeable copper is a highly valuable tool for the diagnosis of Wilson disease

Histological features of liver disease development in the Atp7b −/− mouse: a model of Wilson’s disease

International audienceAims Wilson’s disease (WD) is caused by mutations in the ATP7B gene, resulting in copper accumulation and toxicity in liver and brain tissues. Due to the initial asymptomatic liver involvement, the progression of liver injuries in WD stays primarily unknown. Atp7b−/− knockout mice have been shown to be an appropriate model of WD for liver involvement. Methods A total of 138 Atp7b−/− mice were included and separated into five groups according to age as follows: 6, 20, 39 and 50 weeks without treatment, and 50 weeks with copper chelator treatment from 39 to 50 weeks of age and compared with 101 wild-type (WT) mice at the same stages. The evolution of histological liver lesions was analysed and compared between groups. Results Significant changes were observed in Atp7b−/− mice compared with WT. Copper deposits in hepatocytes appeared as early as 6 weeks but no significant increase over time was observed. Inflammation appeared as early as 6 weeks and progressed henceforth. Lobular and periportal acidophilic bodies appeared after 20 weeks. Significant atypia was also observed at 20 weeks and increased over time to reach a severe stage at 39 weeks. Fibrosis also became apparent at 20 weeks, progressing subsequently to precirrhotic stages at 50 weeks. Copper content, inflammation and fibrosis scores were significantly reduced in the treated group. No bile duct lesions or dysplastic changes were noted. Conclusions Copper accumulation leads to progressive changes in Atp7b−/− mice regarding inflammation, fibrosis and atypia. The severity of liver damage is lessened by chelation therapy

Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations.

International audienceCONTEXT: Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes. OBJECTIVE: Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient. DESIGN: Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA. PATIENTS OR OTHER PARTICIPANTS: A 5-year-old French boy with HHS and his family members participated. RESULTS: The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC. CONCLUSION: The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23

Combined use of creatinine and cystatin C improves the detection of renal dysfunction in children undergoing home parenteral nutrition

International audienceBackground Renal dysfunction can complicate home parenteral nutrition (HPN). The aims were, in the context of pediatric HPN, to assess renal function using the measured glomerular filtration rate (mGFR), determine the most accurate formula(s) to estimate GFR, and identify possible underlying mechanisms of renal impairment.Methods A retrospective study was performed in 2 centers. Patients receiving HPN and aged 2-16 years without medical history of nephropathy were included. GFR was measured using iohexol clearance. Estimated GFR (eGFR) was calculated using creatinine, cystatin C-based, and combined (eGFR(cr+cyst)) Schwartz formulas.Results A total of 36 patients (18 females) were included; they received HPN for 8 (2-16) years. The primary digestive disease was short-bowel syndrome for 16 (44%) patients, gastrointestinal motility disorder for 10 (28%), or congenital diarrhea for 10 (28%). The median (range) mGFR was 99 (33-136) ml/min/1.73 m(2); 9 (25%) patients had mildly decreased mGFR (= 60 ml/min/1.73 m(2)), and 2 (6%) had mildly to severely decreased mGFR (<60 ml/min/1.73 m(2)). The eGFR(cr+cyst) formula was the most accurate and precise to estimate GFR. A significant negative correlation between mGFR and PN duration was found for patients receiving PN for 6-7/7 days (P = .008). Activation of the renin-angiotensin system was identified in 15 of 36 (42%) patients.Conclusion Renal dysfunction was frequent and correlated with the duration of PN only for patients with the most severe intestinal failure. The use of eGFR(cr+cyst) improves its detection in these patients. Chronic dehydration may be an underlying mechanism

A prospective case–control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT

International audienceAbstract Long-term parenteral nutrition (PN) may induce bone complications. Tridimensional bone imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) allow the assessment of both compartmental volumetric densities and microarchitecture. Our aim was to evaluate these parameters in children and teenagers receiving long-term PN. This cross-sectional, case–control study included children older than 9 years undergoing PN for at least 2 years. They were age-, gender- and puberty-matched with healthy controls (1:2). Evaluation included biological assessment of bone metabolism (serum calcium, phosphate, and albumin; urinary calcium and creatinine; 25-OH vitamin D, osteocalcin and PTH), dual X-ray absorptiometry (DXA) and HR-pQCT at the ultradistal tibia and radius. Results are presented as median [range]. Eleven patients (3 girls) with a median age of 16 [9–19] years were included. Bone parameters assessed by HR-pQCT at the ultradistal radius and tibia were similar in patients and controls. Parathyroid hormone (PTH) levels were higher (14 [7–115] vs 16 [12–27]) and osteocalcin levels were lower (44 [15–65] vs 65 [38–142]) in patients than in controls, although within the normal range. Conclusions: there were no differences for compartmental bone densities and microarchitecture in patients undergoing chronic PN. Further longitudinal studies are required to confirm these quite reassuring preliminary results