Variable expressivity of HJV related hemochromatosis: "Juvenile" hemochromatosis?

Juvenile hemochromatosis is a rare autosomal recessive disease due to variants in the Hemojuvelin (HJV) gene. Although biological features mimic HFE hemochromatosis, clinical presentation is worst with massive iron overload diagnosed during childhood. Our study describes clinical features and results of genetic testing for a group of patients initially referred for a hepcidino-deficiency syndrome and for whom HJV hemochromatosis was finally diagnosed. 662 patients with iron overload and high serum transferrin saturation were tested, and five genes (HFE, HJV, HAMP, TFR2, SLC40A1) were sequenced. Among our cohort, ten unrelated patients were diagnosed with HJV hemochromatosis. Genetic testing revealed five previously published and five undescribed variants: p.Arg41Pro, p.His180Arg, p.Lys299Glu, p.Cys361Arg and p.Ala384Val. Surprisingly, this study revealed a late age of onset in some patients, contrasting with the commonly accepted definition of "juvenile" hemochromatosis. Five of our patients were 30 years old or older, including two very late discoveries. Biological features and severity of iron overload were similar in younger and older patients. Our study brings new insight on HJV hemochromatosis showing that mild phenotype and late onset are possible. Genetic testing for HJV variants should thus be performed for all patients displaying a non-p.Cys282Tyr homozygous HFE hemochromatosis with hepcidin deficiency phenotype.

Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

p.Cys282Tyr (C282Y) homozygosity explains most cases of HFE-related hemochromatosis, but a significant number of patients presenting with typical type I hemochromatosis phenotype remain unexplained. We sought to describe the clinical relevance of rare HFE variants in non-C282Y homozygotes. Patients referred for hemochromatosis to the National Reference Centre for Rare Iron Overload Diseases from 2004 to 2010 were studied. Sequencing was performed for coding region and intronic flanking sequences of HFE, HAMP, HFE2, TFR2, and SLC40A1. Nine private HFE variants were identified in 13 of 206 unrelated patients. Among those, five have not been previously described: p.Leu270Argfs*4, p.Ala271Valfs*25, p.Tyr52*, p.Lys166Asn, and p.Asp141Tyr. Our results show that rare HFE variants are identified more frequently than variants in the other genes associated with iron overload. Rare HFE variants are therefore the most frequent cause of hemochromatosis in non-C282Y homozygote HFE patients. Am. J. Hematol. 91:1202-1205, 2016. © 2016 Wiley Periodicals, Inc.

[Bowel preparation : what's new ?]. / Préparation colique : Quoi de neuf?

BACKGROUND: The efficiency of bowel preparation directly affects the quality and the reliability of total colonoscopy. Inadequate bowel cleansing is a common cause of incomplete colonoscopy with a risk of ignoring pre-neoplastic lesions represented primarily as adenomas with a size below centimetre. Due to the numerous factors interfering with preparation, an adapted choice of the type of preparation and the follow-up of diverse methods to optimize bowel preparation allows to improve diagnostic accuracy and to reduce costs while guaranteeing to the patient good tolerabilty and safety. AIM: To report the news about the terms of the bowel preparation for colonoscopy quality and to propose practical ways to optimize it. METHODS: Review of literature and lecture of recommendations. RESULTS: The pre-colonoscopy consultation, prescription of a split dose bowel preparation and a brief time between the last dose of preparation and colonoscopy are the means currently available to optimize bowel preparation. CONCLUSION: A better understanding of terms of bowel preparation and the factors influencing the degree of preparation improve the diagnostic efficacy of colonoscopy especially in the detection and treatment of colorectal cancer.

[Catastrophic antiphospholipid syndrome and rituximab: a new report]. / Syndrome catastrophique et anti-CD20: une nouvelle observation.

BACKGROUND: Catastrophic antiphospholipid syndrome is a distinctly rare dramatic condition characterized by widespread thrombosis of small vessels. Early diagnosis and aggressive therapies are essential in this condition because of its extremely high mortality rate. Therapeutic management include heparine, high dose steroids, cyclophosphamide, plasma exchange, intravenous immunoglobuline, however a number of patients are refractory to treatment. AIM: We review and discuss alternative and emerging treatment options by rituximab for patients who fail or cannot tolerate conventional therapy. CASE-REPORT: A 36-year-old female with a two mounths history of dyspnea, palpitation and chest pain was admitted. Physical examination upon admission revealed a fever, ischemic digital necrosis, scleroderma of the hands and beaking of the nose. Laboratory tests showed normal level of liver enzymes, elevation of creatinine level, lymphopenia, haemolytic anaemia with negative Coombs tests, low platelet count, prolonged partial thromboplastin time. The D-Dimer value was 158 ng/ml. Urinalysis revealed a proteinuria. Antinuclear antibody tests and lupus anticoagulant were strongly positive. Echocardiography revealed severe pulmonary hypertension and pericarditis. There was no pulmonary embolism on thoracic angio tomodensitometry. The diagnosis of catastrophic antiphospholipid antibody syndrome associated with systemic lupus and scleroderma was established. She was treated with anticoagulants, corticotherapy, one pulse of intravenous cyclophosphamide, 2 doses of intravenous immunoglobuline and 5 sessions of plasmapheresis. Because of lack of response 2 doses of 375 mg weekly rituximab i.v. were added but she developed pulmonary embolism, alveolar haemorrhage and she died. CONCLUSION: Effectiveness of Rituximab for the CSAPL should be demonstrated by further studies.

Chronic hepatitis C: treat or wait? A prospective study on reasons for treatment or nontreatment in the era of first-generation protease inhibitors.

BACKGROUND AND AIMS: In many countries, current treatment for patients with chronic hepatitis C involves a combination of peginterferon and ribavirin, associated with a protease inhibitor for hepatitis C virus genotype 1. More recent and efficient less toxic antiviral treatments are now available for some patients. Thus, the decision to treat or to wait is challenging. The aims of this study were to: (a) estimate the proportion of treated patients, (b) evaluate the reasons for this decision, and (c) examine the patients' points-of-view in treatment decision. METHODS: This was a prospective study conducted at three French referral centers between March and June 2013. Epidemiological and virological data, reasons for treatment or nontreatment, and data on the doctors' and patients' choices were collected. RESULTS: A total of 255 patients were analyzed. Only 52.6% of patients with fibrosis of 2 or higher were treated. Treatment uptake was reduced in the following groups: previously treated patients, those with poor tolerance during prior treatment, those with heavy alcohol consumption, and those with hepatocellular carcinoma. Of the cirrhotic patients, 55% were not treated: 51.1% had a contraindication, 22.2% had a previous nonresponse. When treatment was refused by the patient, fear of side effects and professional problems were the most frequently cited reasons (90 and 40%, respectively). CONCLUSION: Patients were treated primarily according to consensus guidelines. However, only 45% of cirrhotic patients were treated. In 7.6% of the cases, the patient refused therapy. This study enabled us to measure the importance of patient choice in medical decision-making. Well-informed patients expected not only more efficient but also well-tolerated therapy.

Non-HFE hemochromatosis: pathophysiological and diagnostic aspects.

Rare genetic iron overload diseases are an evolving field due to major advances in genetics and molecular biology. Genetic iron overload has long been confined to the classical type 1 hemochromatosis related to the HFE C282Y mutation. Breakthroughs in the understanding of iron metabolism biology and molecular mechanisms led to the discovery of new genes and subsequently, new types of hemochromatosis. To date, four types of hemochromatosis have been identified: HFE-related or type1 hemochromatosis, the most frequent form in Caucasians, and four rare types, named type 2 (A and B) hemochromatosis (juvenile hemochromatosis due to hemojuvelin and hepcidin mutation), type 3 hemochromatosis (related to transferrin receptor 2 mutation), and type 4 (A and B) hemochromatosis (ferroportin disease). The diagnosis relies on the comprehension of the involved physiological defect that can now be explored by biological and imaging tools, which allow non-invasive assessment of iron metabolism. A multidisciplinary approach is essential to support the physicians in the diagnosis and management of those rare diseases.