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Wilson disease is a rare inherited disorder of copper metabolism that affects liver and brain due to copper tissue accumulation. The mechanism involved is based on mutations of the ATP7B gene. Children have predominant hepatic manifestations while adult are more often diagnosed by neurological and psychiatric symptoms. However, others features are tubulopathy, articular disorders and hemolytic anemia. We report the diagnostic of Wilson disease in a 14 years old girl and her sibling after investigation of hemolytic anemia, hepatic insufficiency, and hypophosphatemia.

International audience; Adrenal incidentaloma refers to an asymptomatic adrenal mass detected through an imaging procedure performed for reasons unrelated to adrenal dysfunction or suspected dysfunction. In general, adrenal incidentalomas are non-functioning adrenal adenomas, but in some cases, may require therapeutic intervention: eg., adrenocortical carcinoma, pheochromocytoma, primary aldosteronism, cortisol hypersecretion, or adrenal insufficiency. Hormone assessment is crucial to characterize adrenal incidentaloma. Nowadays, various hormone assay methods are available, such as immunoassay and mass spectrometry. However, there are several pitfalls that should be considered: e.g., circadian rhythm, gender/age dependency, preanalytical and analytical issues, and drug interactions. Pharmacological or analytical interference can lead to false serum concentrations and may result in misinterpretation of results and thus inappropriate treatment. The purpose of this review was to study the main interferences that may be observed in the different tumor types of adrenal incidentalomas in order to help physicians in their clinical decision-making and for the overall benefit of patients.; Un incidentalome surrénalien est une masse surrénalienne asymptomatique découverte de façon fortuite par un examen d’imagerie dont l’indication initiale est indépendante d'une pathologie surrénalienne suspectée. La plupart du temps, il s’agit d’adénomes surrénaliens non fonctionnels, mais dans certains cas, une intervention thérapeutique est nécessaire (corticosurrénalome, phéochromocytome, hyperaldostéronisme primaire, hypersécrétion de cortisol, insuffisance surrénalienne, par exemple). Le bilan hormonal est essentiel pour caractériser la fonctionalité d'un incidentalome surrénalien. De nos jours, il existe différentes méthodes de dosages des hormones (techniques immunologiques, spectrométrie de masse..). Il y a, cependant, certains pièges dont il faut tenir compte : le rythme circadien, des corrélations avec l’âge ou le sexe, certaines questions analytiques ou préanalytiques et les interactions médicamenteuses. Les interférences pharmacologiques ou analytiques retrouvées dans ces techniques peuvent être responsables d’erreurs de dosages conduisant à des erreurs d’interprétation, et donc de prise en charge. L’objectif de cette revue est de présenter aux praticiens les principales interférences pouvant être observées dans le cadre du bilan biologique des différents types d’incidentalomes surrénaliens, pour améliorer la décision clinique et la prise en charge des patients.

International audience; Recent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. Using a mouse model of high-fat diet-induced obesity and hyperglycemia, we found a loss of the anti-hyperglcemic effect and insulinotropic activity of 26RFa, accompanied with a marked reduction of its insulin-sensitive effect. Interestingly, this resistance to 26RFa is associated with a down-regulation of the 26RFa receptor in the pancreatic islets, and insulin target tissues. Finally, we observed that the production and release kinetics of 26RFa after an oral glucose challenge is profoundly altered in the high-fat mice. Altogether, the present findings support the view that 26RFa is a key regulator of glucose homeostasis whose activity is markedly altered under obese/hyperglycemic conditions.

Objective Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test. Results 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/GPR103 system is mostly present in the β cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood levels and the BMI, and with various parameters of insulin secretion and insulin resistance. Conclusion The present data suggest an involvement of the 26RFa/GPR103 peptidergic system in the control of human glucose homeostasis.

Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ). Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c). Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [β103(G5)Phe→Ile; HBB: c.310T>A]. The proband is a 38-year-old woman referred to our institution for a moderate but persistent polycythemia without any clinical consequence. As her mother had a similar blood count, a diagnosis of a Hb variant with high oxygen affinity was proposed. The variant was difficult to detect by capillary electrophoresis (CE) and not distinguishable by high performance liquid chromatography (HPLC) and isoelectric focusing. Finally, a heterozygous mutation on the HBB gene corresponding to Hb Saint Nazaire was identified. This case report illustrates that this rare cause of erythrocytosis can be easily under or misdiagnosed unless several Hb separation techniques are used.

International audience; Background: An accurate assessment of septic patients at risk for poor clinical outcomes is challenging for clinicians in the emergency department (ED).Objectives: We aimed to evaluate the prognostic value of procalcitonin (PCT) in septic patients in the ED for predicting death.Results: In a retrospective study, 188 septic patients (median age 63 [IQR 51–80]) of two French university hospitals were included. Patients who deceased within 30 days (20 %, n = 37) presented higher PCT value at admission (median 34.0 µg/L [5.0–71.9]) in comparison with the survivals (median 6.4 µg/L [4.1–13.1], p = 0.0005). ROC curve analysis indicated a moderate AUC of 0.686 [95 % CI 0.613–0.752] and an optimal PCT threshold value at 32.5 [95 % CI 21.8–43.3] µg/L that was associated with a 51 % [34–67] sensitivity, a 96 % [90–98] specificity, a 73 % [52–88] positive predictive value, and a 89 % [83–93] negative predictive value for death. Only 26 patients (14 %) had PCT values above this threshold (19 in the deceased group vs 7 in survival group, p < 0.0001). By multivariate analysis, only three variables remained significantly predictive of the death: personal history of cardiovascular disease (OR 3.1 [1.0–9.4], p = 0.046), the presence of severe sepsis/septic shock in the ER (OR 4.4 [1.3–12.3], p = 0.013), and a PCT level >32.5 µg/L (OR 36.0 [10.0–128.4], p < 0.0001). Similar results were obtained when considering the combined outcome death and/or admission in ICU.Conclusion: Elevated value of PCT at admission has moderate accuracy to identify poor outcome in ED septic patients in daily practice.

Dear Editor, Reports on the analytical evaluation of capillary electrophoresis (CE) for glycated hemoglobin (HbA1c) measurement have already been published [1]. There have been several recent reports concerning the impact of the presence of hemoglobin variants on HbA1c measurement with the CE method. One study focused on the analytical interference of some hemoglobin variants [2], demonstrating that hemoglobin variants S, C, D, and E do not interfere either with HbA1c measurement or the glycation rate of hemoglobin variants, which is equal to the glycation rate of HbA. In a second report, analytical evaluation of CE showed that hemoglobin variant E and β-thalassemia do not affect HbA1c results. Moreover, most hemoglobin variants common to China can be detected by using a CE analyzer, and HbA1c values do not seem to be affected [3]. We report a case of hemoglobin Camperdown (HbCa) detected by using a Capillarys 2 Flex Piercing instrument (C2FP, Sebia, Lisses, France) during HbA1c measurement. A 76-yr-old man receiving follow-up care for type 2 insulin-dependent diabetes was admitted to our hospital for a necrotic wound on the heel. To manage the diabetes, HbA1c was measured on a C2FP instrument in our clinical biology laboratory at Rouen University Hospital, France. The CE software flagged an alarm stating "Atypical profile" with an HbA1c value of 4.2% (22 mmol/mol). We observed an abnormality on the electropherogram (Fig. 1), with a peak of unknown hemoglobin quantified at 3.0% and named fraction 1 by the CE software. There was no other abnormality on the electropherogram. The sample was also tested with a Bio-Rad Variant II analyzer (Bio-Rad, Marnes-la-Coquette, France) in the clinical biology laboratory at Le Havre General Hospital, France, which measured the HbA1c value at 52.2% (547 mmol/mol) because of migration of a probable hemoglobin variant in the HbA1c zone. Concentration of fructosamine (261 µmol/L; 205-260 µmol/L) was just above the reference values, which was not consistent with the two HbA1c values obtained. The patient's last HbA1c measurement was performed in our laboratory 10 yr previously. At that time, we observed a peak of unknown hemoglobin on HPLC (Variant, Bio-Rad), and we were not able to quantify HbA1c. The unknown hemoglobin was identified in the National Hemoglobinopathy Reference Laboratory (Creteil, France) as HbCa [β104Arg→Ser]. Ten years ago, the percentage of HbCa was estimated at 51.5%, which was consistent with a heterozygote patient. We supposed that the unknown fraction 1 on the electropherogram was the glycated fraction of HbCa. We observed that both glycated fractions were clearly separate, unlike HbCa and HbA0, which exactly coeluate, explaining the abnormal value of HbA1c calculated by the CE software. A manual off-line recalculation of the global glycated fractions percentage was performed, by integrating the sum of both peaks instead of HbA1c with the formula for percentage of glycated fractions=(HbA1c+HbCa1c)/(Total HbA0 peak)×100. We then applied the calibration equation of the software, thereby obtaining a value of 6.3% (45 mmol/mol) for global glycated fractions. Fig. 1 Abnormal electropherogram obtained by Capillarys 2 Flex Piercing instrument. Abnormal electropherogram with software alarm "atypical profile" showing a peak of unknown hemoglobin (HbCa1c), which is the glycated form of hemoglobin Camperdown (HbCa). HbCa ... HbCa is a rare variant, first described in 1974 [4], which is not associated with hematological abnormalities. Hemoglobin variants can affect the accuracy of HbA1c measurement, resulting in interference. This interference depends on the type of hemoglobin variant and the method used. Recently, Gaborit et al. [5] published the effects of this variant on HbA1c measurement using HPLC and immunoassay methods. They concluded that it was not possible to measure the exact HbA1c value with the affinity chromatography method. Moreover, immunoassay methods are blind to detecting such variants and probably underestimate HbA1c values. Herein we describe for the first time a case of HbCa interfering with CE HbA1c measurement. The C2FP HbA1c method is not able to differentiate HbA0 from HbCa. The presence of an unknown peak must alert the pathologist. The CE software value is affected by negative bias due to the co-elution of HbCa and HbA0. Manual recalculation seems to yield good results for global glycated fractions, consistent with fructosamine. However, the threshold for HbA1c values must be applied with great care. In fact, the glycated rate of this rare variant has not yet been validated by any publication in the literature. Fructosamine, glycated albumin, or daily capillary blood glucose remain good markers to manage such patients.

A 19-year-old man with DiGeorge syndrome associated with hypoparathyroidism presented with hypercalcemia. He was known to have poor compliance with alfacalcidol and calcium carbonate treatment. Laboratory values are shown in Table 1. Aggressive intravenous hydration with simultaneous administration of calcitonin and bisphosphonates were initiated to lower plasma calcium …

A 9-year-old boy presented to the Dermatology Department for the follow-up of a bullous pemphigoid. This diagnosis had recently been established based on his clinical picture and immunologic test results, and he had begun treatment. He was found to have methemoglobinemia as determined from an arterial blood sample (Table 1). This analysis was …

In March, 2009, a previously healthy 22-year-old woman presented with clinical features of acute bacterial gastroenteritis after returning from India. Shigella sonnei was isolated from a stool sample. Despite appropriate antibiotic treatment with ciprofl oxacin, she continued to have diarrhoea and fl uctuating fever. In September, 2009, she was seen by an infectious disease specialist, who did laboratory investigations that excluded infectious disease. 3 months later, she presented to our emergency department complaining of abdominal pain for 3 days. On examination, she was febrile (39·4°C) and had a palpable mass associated with right upper quadrant pain. She had no weight loss. Her C-reactive protein was 145 mg/L (normal

Sanfilippo syndrome (mucopolysaccharidosis type III, MPS III) is a progressive disorder in which patients are characterized by severe central nervous system degeneration together with mild somatic disease. MPS III results from a deficiency in one of the four enzymes involved in the heparan sulfate degradation, with sulfamidase (SGSH), α-N-acetylglucosaminidase (NAGLU), acetyl-coenzyme A: α-glucosaminide N-acetyltransferase (HGSNAT), and N-acetylglucosamine-6-sulfatase (GNS) being deficient respectively in MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID. Mutation screening using PCR reaction/sequencing analysis on genomic DNA fragments was performed in seven Tunisian index cases with MPS IIIA, three with MPS IIIB and two with MPS IIIC. QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments) analysis was developed for the detection of genomic deletions and duplications in the SGSH gene. These approaches allowed the identification of 11 mutations, 8 of them were novel including a mutation involving the start codon (p.Met1?), one small duplication (p.Leu11AlafsX22), one small deletion (p.Val361SerfsX52) and a large deletion of exon 1 to exon 5 in the SGSH gene, one missense mutation (p.Pro604Leu) and one nonsense mutation (p.Tyr558X) in the NAGLU gene and, finally, one missense mutation (p.Trp627Cys) and one nonsense mutation (p.Trp403X) in the HGSNAT gene.