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In patients with acute intermittent porphyria (AIP), induction of delta aminolevulinic acid synthase 1 (ALAS1) leads to haem precursor accumulation that may cause recurring acute attacks. In a recent phase III trial, givosiran significantly reduced the attack rate in severe AIP patients. Frequent adverse events were injection-site reaction, fatigue, nausea, chronic kidney disease and increased alanine aminotransferase.To describe the efficacy and safety of givosiran based on a personalized medical approach.We conducted a retrospective patient file study in 25 severe AIP patients treated with givosiran in France. We collected data on clinical and biochemical efficacy along with reports of adverse events.Givosiran drastically reduced the attack rate in our cohort, as 96% were attack-free at the time of the study. The sustained efficacy of givosiran in most patients allowed us to personalize dosing frequency. In 42%, givosiran was only given when haem precursor levels were increasing. Our data suggest that givosiran is most effective when given early in the disease course. We confirmed a high prevalence of adverse events. One patient discontinued treatment due to acute pancreatitis. All patients had hyperhomocysteinemia, and all patients with initial homocysteine levels available showed an increase under treatment. In this context, one patient was diagnosed with pulmonary embolism.The sustained effect of givosiran allowed a decrease in dosing frequency without compromising treatment efficacy. The high prevalence of adverse events emphasizes the importance of restricting the treatment to severe AIP and administering the minimum effective dose for each patient.

Points essentiels Le protoxyde d’azote peut entrainer une addiction. Le protoxyde d’azote peut entrainer des accidents graves, voire mortels. Le protoxyde d’azote peut entrainer des complications neurologiques graves avec sequelles (consommations regulieres et importantes, parfois en quantites plus faibles). Tout signe neurologique, survenant chez une personne jeune, doit faire rechercher la consommation de protoxyde d’azote. Tout signe neurologique compatible d’azote avec une atteinte medullaire ou neurologique peripherique survenant chez un usager de protoxyde necessite un avis neurologique rapide et l’arret urgent des consommations. Le protoxyde d’azote peut entrainer l’apparition de thromboses veineuses ou arterielles (en cas d hyperhomocysteinemie majeure). Il est important de rechercher la consommation et d’informer les usagers sur ces risques.

Hepatocellular carcinoma (HCC) is a longstanding issue in clinical practice and metabolic research. New clues in better understanding the pathogenesis of HCC might relate to the metabolic context in patients with citrin (aspartate-glutamate carrier 1) deficiency (CD). Because citrin-deficient liver (CDL) is subject to HCC, it represents a unique metabolic model to highlight the mechanisms of HCC promotion, offering different angles of study than the classical metabolic syndrome/obesity/non-alcoholic fatty liver disease (NAFLD)/HCC study axis. In turn, the metabolic features of HCC could shed light on the pathogenesis of CDL. Among these, HCC-induced re-activation of aralar-1 (aspartate-glutamate carrier 2), physiologically not expressed in the adult liver, might take place in CDL, so gene redundancy for mitochondrial aspartate-glutamate carriers would be exploited by the CDL. This proposed (aralar-1 re-activation) and known (citrate/malate cycle) adaptive mechanisms may substitute for the impaired function in CD and are consistent with the clinical remission stage of CD and CD improvement by medium-chain triglycerides (MCT). However, these metabolic adaptive benefits could also promote HCC development. In CD, as a result of PPARα down-regulation, liver mitochondrial fatty acid-derived acetyl-CoA would, like glucose-derived acetyl-CoA, be used for lipid anabolism and fuel nuclear acetylation events which might trigger aralar-1 re-activation as seen in non-CD HCC. A brief account of these metabolic events which might lead to aralar-1 re-activation in CDL is here given. Consistency of this account for CDL events further relies on the protective roles of PPARα and inhibition of mitochondrial and plasma membrane citrate transporters in non-CD HCC.

An adolescent girl consults a physician for abdominal pain attacks occurring regularly for 2 years. After eliminating gastroenterologic or gynecologic causes, an acute hepatic porphyria is suspected. The pink color of her urine seems consistent with the suspicion of porphyria; however, the urinary profile of porphyrins and its precursors is normal.Une adolescente consulte son médecin pour des crises de douleurs abdominales survenant de manière régulière depuis environ 2 ans. Après avoir éliminé une étiologie gastro-intestinale ou gynécologique, une porphyrie aiguë hépatique est suspectée. Un bilan urinaire est alors réalisé. La coloration rose des urines est en faveur de cette hypothèse, cependant le profil urinaire des porphyrines et de ses précurseurs est normal, excluant une crise aiguë de porphyrie.

Hypersomnia is a rare neurologic disorder characterized by an excessive daytime sleepiness with long naps, despite an undisturbed nocturnal sleep. The impaired daytime alertness and sleep inertia are different from general fatigue. This disorder is often classified as idiopathic. Here, we report the case of a young patient presenting both a mitochondrial disease and a hypersomnia. We discuss the links between the two pathologies and propose to systematically investigate personal and familial mitochondrial features in case of hypersomnia, to offer suitable genetic tests. Conversely, fatigue could be one of the complaints reported by patients with a confirmed mitochondrial disease, which is multifactorial. Sleep quality and somnolence should be examined in these patients as specific treatments exist for this debilitating disorder.

Introduction Triheptanoin provides long-chain fatty acid oxidation disorder (LC-FAOD) patients with an alternative to medium-even-chain triglycerides therapy. Material-methods Retrospective analysis of 18 French LC-FAOD patients benefiting from early access to triheptanoin treatment. Results Eight female and 10 male patients with LC-FAOD (VLCAD, LCHAD, CACT, CPTII and MTP) were treated with triheptanoin for a median duration of 22 months (range: 9–228 months). At last consultation, triheptanoin accounted for 15–35% of their daily caloric intake. In the year following the introduction of triheptanoin, patients reported a reduction of intermittent snacking and nocturnal meals. Three patients, including 1 adult, became free of severe hypoglycaemic events. Ten of 12 paediatric patients and 4 of 6 adult patients reported reduced fatigue with reductions in the number and severity of episodes of myalgia. Of 6 patients, including 1 adult, that had required the use of a wheelchair in the year prior to triheptanoin, all but one no longer required its use. The number of emergency hospitalizations decreased, and none were recorded for paediatric patients during these 12 months. Cumulative annual days of emergency care in the home were reduced from 286 to 51 days in the year before and after initiation, respectively, and 13 patients required no such interventions. Adverse events were limited to digestive issues that dissipated over time. Conclusions Our case-series suggests that long-term treatment of LC-FAOD paediatric and adult patients with triheptanoin is safe and leads to marked improvement of symptoms and an improved quality of life.

Maple syrup urine disease (MSUD) is a rare inborn metabolic disorder, managed with a strict protein‐restricted diet. At any time or age patients may still experience metabolic decompensations, requiring administration of branched chain amino acid (BCAA)‐free formula to reduce leucine levels. This retrospective observational study of 126 decompensation episodes from 54 MSUD patients treated at five centers in France and Germany from 2010 to 2016, describes episodes and outcomes for patients stratified into groups who received enteral/oral or intravenous (IV) BCAA‐free formula, and by pediatric or adult age categories. IV administration of BCAA‐free formula was required in cases of gastric intolerance (33%), refusal to undergo nasogastric tubing (31%), “emergency” (14%) or coma patients (8%), and as prophylaxis before surgery (6%). Overall, mean duration of hospitalization was 6.6 days with oral/enteral BCAA‐free formula and 5.4 days with IV formula. Leucine levels at discharge decreased by a mean of 548.5 μmol/L (69.3%) in the oral/enteral group and 657.2 μmol/L (71.3%) in the IV group. In the pediatric subgroup, there were no marked differences between administration groups on any outcome. In the adult subgroup, mean time to episode resolution was 15.8 days in the oral/enteral group and 7.7 days in the IV group (P = .008); mean duration of hospitalization was 6 days in the oral/enteral group and 4.6 days in the IV group (P = NS). Overall, seven serious adverse events in two patients were reported, of which only nausea and vomiting were treatment related.

International audience; Background: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). Objectives: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. Methods: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. Results: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction

Resume L’echographie en rhumatologie s’est developpee a partir des annees 1990, a la fois pour le diagnostic et le suivi therapeutique, mais aussi dans le developpement de techniques infiltratives echoguidees. Depuis, son utilisation fait partie du quotidien du rhumatologue. Ce chapitre permet de passer en revue les differents aspects des gestes echoguides en rhumatologie : les principales indications, les contre-indications et les effets indesirables a connaitre, ainsi que les modalites pratiques : l’aspect technique et les voies d’abord et le choix du materiel (derives cortisones, aiguilles, sondes).

Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disease due to glucose‐6‐phosphatase deficiency. Chronic kidney disease is a frequent complication that may manifest itself by glomerular lesions and tubular dysfunction from the second decade of life. We report two young GSDIa patients with malignant renal tumor. The first patient was a 25‐year‐old man. He had chronic metabolic imbalance without kidney involvement. The tumor, a type 2 papillary renal carcinoma, was accidentally discovered during follow‐up. The second patient was a 27‐year‐old woman with chronic metabolic imbalance and chronic kidney involvement. The tumor, a grade 2 papillary carcinoma, was accidentally discovered during follow‐up. These two observations are, to date, the first to be reported. We suggest that annual monitoring of kidney imaging in GSDI patients should be systematic to detect renal cancer, from the second decade of life.

Acid sphingomyelinase deficiency (ASMD) is a rare inherited lipid storage disorder caused by a deficiency in lysosomal enzyme acid sphingomyelinase which results in the accumulation of sphingomyelin, predominantly within cells of the reticuloendothelial system located in numerous organs, such as the liver, spleen, lungs, and central nervous system. Although all patients with ASMD share the same basic metabolic defect, a wide spectrum of clinical presentations and outcomes are observed, contributing to treatment challenges. While infantile neurovisceral ASMD (also known as Niemann–Pick disease type A) is rapidly progressive and fatal in early childhood, and the more slowly progressive chronic neurovisceral (type A/B) and chronic visceral (type B) forms have varying clinical phenotypes and life expectancy. The prognosis of visceral ASMD is mainly determined by the association of hepatosplenomegaly with secondary thrombocytopenia and lung disease. Early diagnosis and appropriate management are essential to reduce the risk of complications and mortality. The accessibility of the new enzyme replacement therapy olipudase alfa, a recombinant human ASM, has been expedited for clinical use based on positive clinical data in children and adult patients, such as improved respiratory status and reduced spleen volume. The aim of this article is to share the authors experience on monitoring ASMD patients and stratifying the severity of the disease to aid in care decisions.

Nitrous oxide (N

International audience; For the first time the glycosylation of a patient with a MPI-CDG during pregnancy is monitored. MPI-CDG, is characterised by a deficiency in mannose-6-phosphate isomerase (MPI) leading to a reduced pool of glycosylation precursors, impairing the biosynthesis of N-glycans leading to N-glycosylation defects. The abnormal N-glycosylation profile with an elevation of asialotransferrin and disialotransferrin, typical of CDG type I, is assessable by transferrin isoelectrofocusing. Oral D-mannose supplementation for MPI-CDG patients has been widely used and improves clinical manifestations. The glycosylation of a MPI-CDG patient during pregnancy without mannose supplementation was studied using carbohydrate deficient transferrin (CDT) assay, transferrin isoelectrofocusing (IEF) and mass spectrometry of total serum N-glycans. A general improvement of the glycosylation profile of the patient due to a better transfer of the glycan precursors as well as an increase of the triantennary glycans (and sialylation) was observed. In conclusion, in the absence of mannose supplementation, the previously observed glycosylation abnormality of the MPI-CDG patient was corrected. The molecular mechanism underlying this N-glycosylation rescue during MPI-CDG pregnancy further needs to be investigated.

Lipodystrophy syndromes (LS) constitute a group of rare diseases of the adipose tissue, characterized by a complete or selective deficiency of the fat mass. These disorders are associated with important insulin resistance, cardiovascular and metabolic comorbidities that impact patient's survival and quality of life. Management is challenging and includes diet, physical activity, and specific pharmacological treatment of LS-associated comorbidities. Because of a common pathophysiology involving decreased concentration of the adipokine leptin, efforts have been made to develop therapeutic strategies with leptin replacement therapy. Metreleptin, a recombinant human leptin analogue, has been proposed in hypoleptinemic patients since the beginning of 2000's. The treatment leads to an improvement in metabolic parameters, more important in generalized than in partial LS forms. In this review, the current knowledge about the development of the drug, its outcomes in the treatment of lipodystrophic patients as well as the peculiarities of its use will be presented.

BACKGROUND: Urea cycle disorders (UCD) are rare diseases that usually affect neonates or young children. During decompensations, hyperammonemia is neurotoxic, leading to severe symptoms and even coma and death if not treated rapidly. AIMS: Description of a cohort of patients with adult onset of UCDs. METHODS: Multicentric, retrospective and descriptive study of French adult patients with a diagnosis after 16 years of age of UCDs due to a deficiency in one of the 6 enzymes (arginase, ASL, ASS, CPS1, NAGS, OTC) or the two transporters (ORNT1 or citrin). RESULTS: Seventy-one patients were included (68% female, 32% male). The diagnosis was made in the context of (i) a metabolic decompensation (42%), (ii) family history (55%), or (iii) chronic symptoms (3%). The median age at diagnosis was 33 years (range 16-86). Eighty-nine percent of patients were diagnosed with OTC deficiency, 7% CPS1 deficiency, 3% HHH syndrome and 1% argininosuccinic aciduria. For those diagnosed during decompensations (including 23 OTC cases, mostly female), 89% required an admission in intensive care units. Seven deaths were attributed to UCD - 6 decompensations and 1 epilepsy secondary to inaugural decompensation. CONCLUSION: This is the largest cohort of UCDs diagnosed in adulthood, which confirms the triad of neurological, gastrointestinal and psychiatric symptoms during hyperammonemic decompensations. We stress that females with OTC deficiency can be symptomatic. With 10% of deaths in this cohort, UCDs in adults remain a life-threatening condition. Physicians working in adult care must be aware of late-onset presentations given the implications for patients and their families. This article is protected by copyright. All rights reserved.

Objective The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants. Methods A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue. Results We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction. Conslusions Biallelic LIPE null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target.

International audience; Mannose phosphate isomerase MPI-CDG (formerly CDG-1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D-mannose. We retrospectively reviewed long-term outcomes of patients with MPI-CDG, all but one of whom were treated with D-mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D-mannose treatment. Nine patients were diagnosed with MPI-CDG at a median age of 3 months. The presenting symptoms were diarrhea (n = 9), hepatomegaly (n = 9), hypoglycemia (n = 8), and protein loosing enteropathy (n = 7). All patients survived except the untreated one who died at 2 years of age. Oral D-mannose was started in eight patients at a median age of 7 months (mean 38 months), with a median follow-up on treatment of 14 years 9 months (1.5-20 years). On treatment, two patients developed severe portal hypertension, two developed venous thrombosis, and 1 displayed altered kidney function. Poor compliance with D-mannose was correlated with recurrence of diarrhea, thrombosis, and abnormal biological parameters including coagulation factors and transferrin profiles. Liver fibrosis persisted despite treatment, but two patients showed improved liver architecture during follow-up. This study highlights (i) the efficacy and safety of D-mannose treatment with a median follow-up on treatment of almost 15 years (ii) the need for life-long treatment (iii) the risk of relapse with poor compliance, (iii) the importance of portal hypertension screening (iv) the need to be aware of venous and renal complications in adulthood.

International audience

International audience; Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves' disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis.

Resume La loi francaise autorise les osteopathes et les chiropracteurs, ni medecins ni masseurs-kinesitherapeutes, a pratiquer des manipulations vertebrales sous certaines conditions. Compte-tenu du developpement tous azimuts des soins manuels en France, cet article a pour but de presenter une synthese narrative de litterature sur les manipulations vertebrales pratiquees chez l’adulte dans le traitement des lombalgies non specifiques aigues et chroniques. Quatorze revues systematiques dont dix avec meta-analyses ont ete incluses. Les resultats de ces revues sont souvent contradictoires et decevants d’un point de vue pratique. Les manipulations vertebrales lato sensu ont une efficacite faible avec des effets tres principalement a court terme sur la reduction de la douleur ou l’amelioration des indices algo-fonctionnels dans le traitement des lombalgies. L’heterogeneite des definitions des lombalgies et des manipulations vertebrales est la premiere source de discordance entre auteurs. L’attention devrait etre attiree dans le futur, sur une meilleure evaluation interculturelle des pratiques et plus de recherches integrant des methodologies rigoureuses par sous-groupes repondant a des regles de prediction clinique.

We report herein the case of a patient with low blood levels of different hormones during a systemic capillary leak syndrome (Clarkson’s disease) attack.

ZAP-70SKG, Il17a-deficient SKG, and BALB/c female mice were infected with C muridarum or C muridarum luciferase in the genitals. C muridarum dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti-tumor necrosis factor (anti-TNF) and anti-interleukin-23p19 (anti-IL-23p19) were administered after infection or arthritis onset. Gene expression of Hspa5, Tgtp1, Il23a, Il17a, Il12b, and Tnf was compared in SKG mice and BALB/c mice.One week following infection with C muridarum, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried C muridarum DNA to the spleen. C muridarum load was higher in SKG mice than in BALB/c mice. Macrophage depletion was shown to reduce C muridarum load and prevent development of arthritis. Compared with BALB/c mice, expression of Il23a and Il17a was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti-IL-23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was overexpressed in the joints of SKG mice within 1 week postinfection, and persisted beyond the first week. TNF inhibition during infection or at arthritis onset suppressed the development of arthritis. Levels of endoplasmic reticulum stress were constitutively increased in the joints of SKG mice but were induced, in conjunction with immunity-related GTPase, by C muridarum infection in the uterus.C muridarum load is higher in SKG mice than in BALB/c mice. Whereas proinflammatory IL-23 produced by neutrophils contributes to the initiation of C muridarum-mediated ReA, macrophage depletion reduces C muridarum dissemination to other tissues, tissue burden, and the development of arthritis. TNF inhibition was also shown to suppress arthritis development. Our data suggest that enhanced bacterial dissemination in macrophages of SKG mice drives the TNF production needed for persistent arthritis.

International audience; Backgroud: Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity.Methods: Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients.Results: We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p

Introduction les etiologies d’elevation de l’homocysteine totale plasmatique (HCYt > 14 μmol/L) sont diverses. Une hyperhomocysteinemie (HHCY) dite intermediaire (> 50 μmol/L) et surtout majeure (> 100 μmol/L) peut-etre revelatrice d’une maladie genetique ou acquise. Methode Etude descriptive et retrospective, apres extraction nominative par le laboratoire des taux d’HCYt ≥ 50 μmol/L, de la naissance a l’âge adulte, entre le 1er janvier 2014 et le 31 mars 2020 (CHU de Lille). L’objectif primaire est de decrire les etiologies retenues des valeurs d’HCYt ≥ 50 μmol/L. L’objectif secondaire est d’identifier le contexte clinique ayant conduit au dosage. Resultats Deux cent quatre vingt six sujets (23 enfants et 263 adultes) presentent une HCYt ≥ 50 μmol/L. Chez l’enfant, les HHCY sont d’origine: genetique (n = 12) par deficits en cystathionine beta-synthase (CBS), methylene-tetrahydrofolate reductase, cobalamines ou deficit hereditaire en facteur intrinseque; Carentielle (n = 7); autres (n = 4). Chez l’adulte, les HHCY sont d’origine: genetique seulement dans 3,4 % des cas (deficits en CBS essentiellement); majoritairement carentielle 45 % (vitamines B12 et/ou B9 ± B6); Insuffisance renale (DFG ≥ 4) 25 % ; medicamenteuse/toxique (N2O) 7 %; non identifiee 18 %. Les indications principales du dosage de l’HCY etaient la survenue d’un evenement thrombotique (37,7 %), l’exploration de troubles cognitifs (15,2 %) ou de troubles neurologiques (9,2 %). Conclusion Les hyperhomocysteinemies ≥ 50 μmol/L sont essentiellement d’origine carentielle et genetique, s’accompagnent d’un risque thrombotique mais sont traitables. Une collaboration entre cliniciens et biologistes est donc indispensable pour optimiser la demarche diagnostique et guider la prise en charge therapeutique.

International audience

Laparoscopic adrenalectomy (LA) has become the standard technique for most indications. The aim of this study was to determine the predictive factors of intra- and postoperative complications in order to inform the orientation of patient to a surgeon with more experience in adrenal surgery. From January 1994 to December 2013, 520 consecutive patients benefited from LA at Huriez Hospital, Lille, France. Each complication was graded according to the Dindo–Clavien-grade scale. The predictive factors of complications were determined by logistic regression. Fifty-two surgeons under the supervision of 5 senior surgeons (individual experience >30 LA) participated. Postoperative complications with a grade of ≥2 occurred in 52 (10 %) patients (29 (5.6 %) medical, 19 (3.6 %) surgical, and 4 (0.8 %) mixed complications) leading to 12 (2.3 %) reoperations. There was no postoperative death. Intraoperative complication happened in 81 (15.6 %) patients responsible for conversion to open adrenalectomy (OA) [odds ratio (OR) 13.9, CI 95 % 4.74–40.77, p

Cerebrotendineous xanthomatosis (CTX) is an autosomal recessive disorder of bile acids synthesis. Patients may present with a variety of clinical manifestations: bilateral cataract and chronic diarrhea during childhood, then occurrence of neurological debilitating symptoms in adulthood (cognitive decline, motor disorders). Plasma cholestanol is used as a diagnostic marker of CTX, and to monitor the response to the treatment. Current treatment for CTX is chenodeoxycholic acid (CDCA), which was reported to improve and/or stabilize clinical status and decrease levels of plasma cholestanol. Rare published reports have also suggested a potential efficacy of cholic acid (CA) in patients with CTX. In this retrospective Franco-Belgian multicentric study, we collected data from 12 patients treated with CA, evaluating their clinical status, cholestanol levels and adverse effects during the treatment period. The population was divided in two subgroups: treatment-naive (who never had CDCA prior to CA) and non-treatment-naive patients (who had CDCA prior to CA introduction). We found that treatment with CA significantly and strongly reduced cholestanol levels in all patients. Additionally, 10 out of 12 patients clinically improved or stabilized with CA treatment. Worsening was noted in one treatment-naive patient and one non-treatment-naive patient, but both patients experienced similar outcomes with CDCA treatment as well. No adverse effects were reported from patients with CA treatment, whereas elevated transaminases were observed in some patients while they were treated with CDCA. In conclusion, these findings suggest that CA may be a suitable alternative treatment for CTX, especially in patients with side effects related to CDCA.

Early Access: NOV 2019; International audience; OBJECTIVE: Phenylketonuria (PKU) is a rare autosomal recessive disease characterised by high plasma phenylalanine levels inducing, if untreated, serious neurological manifestations in children but also, rarely, in adults who stopped their diet. The objective of the study was to describe the neurological manifestations observed in adults with PKU. METHODS: We analysed cases reported in French reference centres for inborn errors of metabolism and cases already reported in the literature. RESULTS: We report 8 new cases of neurological manifestations and 22 cases in the literature, which occurred in adult PKU patients, associated with chronic or rapid increase of phenylalanine levels, mostly when strict low-phenylalanine diet was stopped early in life. Neurological symptoms consisted in cerebellar ataxia, tremor, brisk reflexes, visual loss, sensory manifestations, and/or headaches. Visual loss was more frequent in the new cases (4/8) of the present series than in the literature (4/22). These neurological complications were associated with leucopathy on brain magnetic resonance imaging (27/29). The start of a low-phenylalanine diet improved or fully reversed neurological manifestations, even in patients with late diagnosis during adulthood. CONCLUSION: Neurological manifestations can complicate PKU in adult patients with elevated phenylalanine levels, after long or short period of diet discontinuation. Neurologists should be aware of this diagnosis, and measure phenylalaninemia in case of neurological symptoms associated with non-specific leucopathy on brain MRI. PKU patients should be systematically encouraged to continue their diet and their medical follow-up to avoid neurological complications.

Resume L’arthrite reactionnelle complique parfois les infections digestives a certains bacilles Gram negatifs, tels que Salmonella, Yersinia, Shigella et Campylobacter. De maniere moins frequente, des arthrites inflammatoires ont egalement ete decrites suivant une infection par Clostridium difficile. Les mecanismes moleculaires de la maladie et notamment le role du HLA-B27 ont ete precises ces dernieres annees. Cependant, peu d’etudes ont specifiquement evalue l’efficacite des traitements de fonds et c’est pourquoi les strategies therapeutiques sont grandement calquees sur celles des autres spondyloarthrites. L’objectivation de la persistance des bacteries et la dissemination de signaux de danger avaient initialement fourni un rationnel a l’emploi d’antibiotherapie, avec des resultats contradictoires selon les etudes. Nous reviendrons sur les hypotheses physiopathologiques ainsi que la prise en charge therapeutique de ces arthrites reactionnelles, en s’appuyant sur les donnees de la litterature.