Publications by authors named "Claire Douillard"

40 Publications

Clinical outcomes in a series of 18 patients with long chain fatty acids oxidation disorders treated with triheptanoin for a median duration of 22 months.

Mol Genet Metab 2021 Feb 10. Epub 2021 Feb 10.

CHU de Lyon, Centre de Biologie et de Pathologie Est, Unité Maladies Héréditaires du Métabolisme, Service de Biochimie et Biologie Moléculaire, Bron, France.

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.
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http://dx.doi.org/10.1016/j.ymgme.2021.02.003DOI Listing
February 2021

Chlamydia-infected Macrophages mediate Interleukin-23 and Tumor Necrosis Factor-driven Reactive Arthritis in SKG Mice.

Arthritis Rheumatol 2021 Jan 16. Epub 2021 Jan 16.

Univ. Grenoble Alpes, GREPI TIMC-IMAG, UMR 5525, 38000, Grenoble, France.

Objective: ZAP-70 BALB/c (SKG) mice develop reactive arthritis (ReA) after Chlamydia muridarum (Cmu) infection. Since intracellular pathogens enhance their replicative fitness in stressed host cells, we examined how myeloid cells taking up Cmu drive arthritis.

Methods: Female SKG, Il17a-deficient SKG and BALB/c mice were genitally infected with Cmu or Cmu Luciferase. Cmu dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti-TNF, anti-IL-23p19 were administered after infection or arthritis onset. Hspa5, Tgtp1, Il23a, Il17a, Il12b and Tnf expression was compared in SKG and BALB/c mice.

Results: One-week post infection, macrophages and neutrophils infiltrated the uterus; both carried Cmu DNA to the spleen. Cmu load was higher in SKG than BALB/c. Macrophage depletion reduced Cmu load and prevented arthritis. Compared with BALB/c, expression of Il23a and Il17a was increased in SKG uterine and splenic neutrophils. Anti-IL-23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was over-expressed in SKG joints within one-week post infection and persisted. TNF inhibition during infection or at arthritis onset suppressed arthritis. Endoplasmic reticulum stress was constitutively increased in SKG joints but was induced, with immunity-related GTPase, by Cmu infection in uterus.

Conclusion: The load of Cmu is higher in SKG than BALB/c mice. While proinflammatory IL-23 produced by neutrophils contributes to the initiation of Cmu-mediated ReA, macrophage depletion reduces Cmu dissemination to other tissues, tissue burden, and arthritis. TNF inhibition suppresses arthritis. Our data suggest that enhanced bacterial dissemination in SKG macrophages drives TNF production required for persistent arthritis.
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http://dx.doi.org/10.1002/art.41653DOI Listing
January 2021

Very High Plasma Homocysteine without Malnutrition or Inherited Disorder.

Clin Chem 2020 Nov;66(11):1468-1469

CHU Lille, Service d'Hormonologie, Métabolisme, Nutrition et Oncologie, Lille, France.

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http://dx.doi.org/10.1093/clinchem/hvaa070DOI Listing
November 2020

LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells.

Eur J Endocrinol 2021 Jan;184(1):155-168

Sorbonne Université, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France.

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.
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http://dx.doi.org/10.1530/EJE-20-1013DOI Listing
January 2021

Long term outcome of MPI-CDG patients on D-mannose therapy.

J Inherit Metab Dis 2020 11 9;43(6):1360-1369. Epub 2020 Aug 9.

Inserm U1151, Institut Necker Enfants-Malades, Paris, France.

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.
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http://dx.doi.org/10.1002/jimd.12289DOI Listing
November 2020

Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.

PLoS One 2020 22;15(5):e0233460. Epub 2020 May 22.

Internal Medicine Department, Reference Center for Lysosomal Storage Disorders, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France.

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 <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI.

Conclusion: Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233460PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244174PMC
August 2020

Low hormone levels during an attack of systemic capillary leak syndrome normalizing after treatment.

Horm Mol Biol Clin Investig 2020 May 20;41(3). Epub 2020 May 20.

Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez, Service D'Endocrinologie-Diabétologie-Métabolisme, 59037, Lille, France.

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.
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http://dx.doi.org/10.1515/hmbci-2020-0004DOI Listing
May 2020

Rare causes of hypoglycemia in adults.

Ann Endocrinol (Paris) 2020 Jun 10;81(2-3):110-117. Epub 2020 Apr 10.

Endocrinology, diabetology, metabolism department, Lille university hospital, Lille, France; Inserm U1190 translational research in diabetes, Lille, France; European genomic institute for diabetes EGID, Lille, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ando.2020.04.003DOI Listing
June 2020

Papillary renal cell carcinoma in two young adults with glycogen storage disease type Ia.

JIMD Rep 2020 Mar 29;52(1):17-22. Epub 2020 Jan 29.

APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique Clamart France.

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.
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http://dx.doi.org/10.1002/jmd2.12096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052693PMC
March 2020

Neurological manifestations in adults with phenylketonuria: new cases and review of the literature.

J Neurol 2020 Feb 7;267(2):531-542. Epub 2019 Nov 7.

Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie C, 69677, Bron Cedex, France.

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.
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http://dx.doi.org/10.1007/s00415-019-09608-2DOI Listing
February 2020

Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults.

J Neurol 2019 Aug 21;266(8):2043-2050. Epub 2019 May 21.

Neurology Department, Reference Center for Lysosomal Diseases, Neurogenetics and Metabolism Unit, Hôpital Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013, Paris, France.

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-naïve patient and one non-treatment-naïve 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.
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http://dx.doi.org/10.1007/s00415-019-09377-yDOI Listing
August 2019

Foetal exposure to mitotane/Op'DDD: Post-natal study of four children.

Clin Endocrinol (Oxf) 2018 12 16;89(6):805-812. Epub 2018 Oct 16.

Department of Reproductive Endocrinology, Univ Paris Sud, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin Bicêtre, France.

Objective: Mitotane/Op'DDD is used in the treatment of adrenocortical carcinoma and for other causes of hypercortisolism. Mitotane inhibits cortisol secretion and displays adrenolytic and antitumor actions. This compound is a metabolite of the pesticide and endocrine disruptor DDT (dichlorodiphenyltrichloroethane) and is classified among teratogenic compounds worldwide. However, little is known about its effects on human development.

Design: The outcome of four children exposed to mitotane during their intrauterine life was examined.

Patients: Patients having conceived while taking mitotane, or with detectable mitotane plasma levels, were retrospectively recruited via the French COMETE and FIRENDO networks.

Measurements: Mitotane in maternal plasma, adrenocortical hormones in children.

Results: Three women treated with mitotane gave birth to four children. During early pregnancy, all patients had detectable mitotane plasma levels (0.9, 2.4 and 6.7 mg/L, respectively). During pregnancy, no foetal malformations were detected. The four exposed newborns presented at birth with apparently normal adrenal function and genitalia. One twin female had a low birthweight. Evaluation at birth and after 3 months, 2 years and 7 years of follow-up showed no significant neurological abnormality. Evaluation of adrenocortical functions showed no cortisol deficiency.

Conclusions: Unexpectedly, exposure of these four children to mitotane during foetal life seemed to have no clear teratogenic effect. However, considering the sub-therapeutic mitotane concentrations used here, the small number of cases, and because long-term follow-up is unknown, we strongly advise not to take mitotane during pregnancy and still recommend avoiding pregnancy, at least as long as mitotane plasma levels remain detectable.
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http://dx.doi.org/10.1111/cen.13854DOI Listing
December 2018

Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY.

Orphanet J Rare Dis 2018 07 31;13(1):127. Epub 2018 Jul 31.

Sorbonne Université, INSERM, UMR 974, Centre of Research in Myology, Association Institut de Myologie, Pitié-Salpêtrière University Hospital, 75013, Paris, France.

Background: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies (ERT) have been available. We aimed to determine the epidemiology and the functional characteristics of anti-drug antibodies. Patients from the French multicenter cohort FFABRY (n = 103 patients, 53 males) were prospectively screened for total anti-agalsidase IgG and IgG subclasses with a home-made enzyme-linked immunosorbent assay (ELISA), enzyme-inhibition assessed with neutralization assays and lysoGb3 plasma levels, and compared for clinical outcomes.

Results: Among the patients exposed to agalsidase, 40% of men (n = 18/45) and 8% of women (n = 2/25) had antibodies with a complete cross-reactivity towards both ERTs. Antibodies developed preferentially in men with non-missense GLA mutations (relative risk 2.88, p = 0.006) and classic phenotype (58.6% (17/29) vs 6.7% (1/16), p = 0.0005). Specific anti-agalsidase IgG1 were the most frequently observed (16/18 men), but the highest concentrations were observed for IgG4 (median 1.89 μg/ml, interquartile range (IQR) [0.41-12.24]). In the men exposed to agalsidase, inhibition was correlated with the total IgG titer (r = 0.67, p < 0.0001), especially IgG4 (r = 0.75, p = 0.0005) and IgG2 (r = 0.72, p = 0.001). Inhibition was confirmed intracellularly in Fabry patient leucocytes cultured with IgG-positive versus negative serum (median: 42.0 vs 75.6%, p = 0.04), which was correlated with IgG2 (r = 0.67, p = 0.017, n = 12) and IgG4 levels (r = 0.59, p = 0.041, n = 12). Plasma LysoGb3 levels were correlated with total IgG (r = 0.66, p = 0.001), IgG2 (r = 0.72, p = 0.004), IgG4 (r = 0.58, p = 0.03) and IgG1 (r = 0.55, p = 0.04) titers. Within the classic group, no clinical difference was observed but lysoGb3 levels were higher in antibody-positive patients (median 33.2 ng/ml [IQR 20.6-55.6] vs 12.5 [10.1-24.0], p = 0.005).

Conclusion: Anti-agalsidase antibodies preferentially develop in the severe classic Fabry phenotype. They are frequently associated with enzyme inhibition and higher lysoGb3 levels. As such, they could be considered as a hallmark of severity associated with the classic phenotype. The distinction of the clinical phenotypes should now be mandatory in studies dealing with Fabry disease and its current and future therapies.
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http://dx.doi.org/10.1186/s13023-018-0877-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069887PMC
July 2018

Hyperinsulinemic hypoglycemia without insulinoma: Think of activating glucokinase mutation.

Presse Med 2018 Jun 17;47(6):595-597. Epub 2018 Mar 17.

Lille University Hospital, C. Huriez Hospital, Endocrinology and Metabolism Department, 1, rue Polonovski, 59037 Lille cedex, France; INSERM U1190 Translational Research in Diabetes, 59037 Lille, France; E.G.I.D - FR3508 European Genomic Institute for Diabetes, 59037 Lille, France. Electronic address:

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http://dx.doi.org/10.1016/j.lpm.2018.02.015DOI Listing
June 2018

Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency.

Mol Genet Metab 2018 04 12;123(4):441-448. Epub 2018 Feb 12.

Department of Biochemistry and Molecular Biology, Laboratory of Endocrinology, Metabolism-Nutrition, Oncology, Biology Pathology Center, CHRU Lille, 59037 Lille, France; Univ. Lille, RADEME - Maladies RAres du Développement et du Métabolisme: du phénotype au génotype et à la Fonction, Lille, EA 7364, France; Inserm, Lille, France. Electronic address:

Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in this profile is not exclusive of CPT2 deficiency. Our retrospective study reports clinical and biological data in a cohort of 11 patients with circulating acylcarnitine profile unconclusive enough for a specific diagnosis orientation. In these patients, CPT2 gene studies was prompted by prior fluxomic explorations of mitochondrial β-oxidation on intact whole blood cells incubated with pentadeuterated ([16-H, 15-H])-palmitate. Clinical indication for fluxomic explorations was at least one acute rhabdomyolysis episode complicated, in 5 of 11 patients, by acute renal failure. Major trigger of rhabdomyolysis was febrile infection. In all patients, fluxomic data indicated deficient CPT2 function showing normal deuterated palmitoylcarnitine (C16-Cn) formation rates associated with increased ratios between generated C16-Cn and downstream deuterated metabolites (Σ deuterated C2-Cn to C14-Cn). Subsequent gene studies showed in all patients pathogenic gene variants in either homozygous or compound heterozygous forms. Consistent with literature data, allelic frequency of the c.338C > T[p.Ser113Leu] mutation amounted to 68.2% in our cohort. Other missense mutations included c.149C > A[p.Pro50His] (9%), c.200C > G[p.Ala200Gly] (4.5%) and previously unreported c.1171A > G[p.ser391Gly] (4.5%) and c.1420G > C[p.Ala474Pro] (4.5%) mutations. Frameshift c.1666-1667delTT[p.Leu556val*16] mutation (9%) was observed in two patients unknown to be related.
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http://dx.doi.org/10.1016/j.ymgme.2018.02.005DOI Listing
April 2018

Erratum to: Laparoscopic adrenalectomy by transabdominal lateral approach: 20 years of experience.

Surg Endosc 2017 07;31(7):2752

Department of General and Endocrine Surgery, CHU Lille, Rue Michel Polonovski, 59000, Lille, France.

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http://dx.doi.org/10.1007/s00464-017-5437-9DOI Listing
July 2017

Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants.

Clin Chim Acta 2017 Aug 19;471:101-106. Epub 2017 May 19.

Department of Biochemistry and Molecular Biology, Laboratory of Hormonology, Metabolism-Nutrition & Oncology (HMNO), Center of Biology and Pathology (CBP) Pierre-Marie Degand, CHRU Lille, France; Univ. Lille, EA 7364 - RADEME - Maladies RAres du Développement et du Métabolisme: du phénotype au génotype et à la Fonction, Lille, France; Inserm, Lille, France. Electronic address:

Background: Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear.

Methods: De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16-H,15-H-palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a β-oxidation disorder.

Results: Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G>A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G>A, 2 compound heterozygous for c.625G>A/c.511C>T).

Conclusion: Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal β-oxidation consistent with known altered kinetics of these variants.
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http://dx.doi.org/10.1016/j.cca.2017.05.026DOI Listing
August 2017

Comparison of fluid balance and hemodynamic and metabolic effects of sodium lactate versus sodium bicarbonate versus 0.9% NaCl in porcine endotoxic shock: a randomized, open-label, controlled study.

Crit Care 2017 May 19;21(1):113. Epub 2017 May 19.

CHU Lille, Centre de Réanimation, F-59000, Lille, France.

Background: Sodium lactate has been shown to improve hemodynamics and avoid fluid overload. The objective of this study was to confirm a beneficial effect on fluid balance with sodium lactate infusion and to specify whether the advantage of lactate is related to a negative chloride balance, its particular metabolism, or simply its energy load.

Methods: This was an interventional, randomized, open-label, controlled experimental study. Fifteen female "large white" pigs (2 months old) were challenged with intravenous infusion of Escherichia coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); and a hypertonic control group, with the same amount of osmoles and sodium as the SL group, received sodium bicarbonate 8.4% (SB group). In order to provide the same energy load in the three groups, control groups were perfused with an equivalent energy supply. Statistical analysis was performed with non-parametric tests and the Dunn correction for multiple comparisons at p < 0.05.

Results: Fluid and chloride balance, hemodynamics, oxygenation markers, and microcirculatory parameters were measured over a 5-h period. Cumulative fluid balance was significantly lower in the SL group (550 (415-800) mL; median (interquartile range)) compared to the NC group (1100 (920-1640) mL, p = 0.01) and the SB group (935 (790-1220) mL, p = 0.03). Hemodynamics, cardiac efficiency, and microcirculation were significantly enhanced in the SL group, resulting in a significant improvement in oxygen delivery (SL group 417 (305-565) mL/min/m at 300 min versus the NC (207 (119-272) mL/min/m, p = 0.01) and the SB (278, (211-315) mL/min/m, p = 0.03) groups). Oxygenation markers (arterial oxygen partial pressure (PaO)/inspired oxygen fraction (FiO), mixed venous oxygen saturation (SvO), and venoarterial carbon dioxide tension difference (Pv-aCO) were enhanced with sodium lactate infusion. Chloride balance was equivalent in both hypertonic groups and significantly reduced compared to the NC group.

Conclusion: Sodium lactate infusion improves fluid balance and hemodynamics. The advantage of lactate does not seem to be explained by its energy load or by the induced negative chloride balance with subsequent water movements.
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http://dx.doi.org/10.1186/s13054-017-1694-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438514PMC
May 2017

A fast method for high resolution oxymetry study of skeletal muscle mitochondrial respiratory chain complexes.

Anal Biochem 2017 07 26;528:57-62. Epub 2017 Apr 26.

Department of Biochemistry and Molecular Biology, Laboratory of Hormonology, Metabolism-Nutrition & Oncology (HMNO), Center of Biology and Pathology (CBP) Pierre-Marie Degand, CHRU Lille, France; Univ. Lille, EA 7364 - RADEME - Maladies RAres du Développement et du Métabolisme: du phénotype au génotype et à la Fonction, Lille, France; Inserm, Lille, France. Electronic address:

High resolution oxymetry study (HROS) of skeletal muscle usually requires 90-120 min preparative phase (dissection, permeabilization and washing). This work reports on the suitability of a rapid muscle preparation which by-passes this long preparation. For a few seconds only, muscle biopsy from pigs is submitted to gentle homogenization at 8000 rotations per minute using an ultra-dispersor apparatus. Subsequent HROS is performed using FCCP instead of ADP, compounds crossing and not plasma membrane, respectively. This simplified procedure compares favorably with classical (permeabilized fibers) HROS in terms of respiratory chain complex activities. Mitochondria from cells undergoing ultradispersion were functionally preserved as attested by relative inefficacy of added cytochrome C (not crossing intact mitochondrial outer membrane) to stimulate mitochondrial respiration. Responsiveness of respiration to ADP (in the absence of FCCP) suggested that these intact mitochondria were outside cells disrupted by ultradispersion or within cells permeated by this procedure.
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http://dx.doi.org/10.1016/j.ab.2017.04.015DOI Listing
July 2017

Biomarkers for outcomes of spondyloarthritis.

Joint Bone Spine 2017 07 24;84(4):385-387. Epub 2017 Feb 24.

GREPI-UGA EA7408C, clinique universitaire de rhumatologie, CHUGA, hôpital Sud, avenue de Kimberley, 38130 Échirolles, France.

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http://dx.doi.org/10.1016/j.jbspin.2017.02.004DOI Listing
July 2017

Laparoscopic adrenalectomy by transabdominal lateral approach: 20 years of experience.

Surg Endosc 2017 07 10;31(7):2743-2751. Epub 2016 Nov 10.

Department of General and Endocrine Surgery, CHU Lille, Rue Michel Polonovski, 59000, Lille, France.

Background: 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.

Methods: 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.

Results: 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 < 0.001]. History of upper mesocolic or retroperitoneal surgery was predictive of intraoperative complication (OR 2.02, 1.05-3.91, p = 0.036). Lesion diameter ≥45 mm was predictive of intraoperative complication (OR 1.94, 1.19-3.15, p = 0.008), conversion to OA (OR 7.46, 2.18-25.47, p = 0.001), and adrenal capsular breach (OR 4.416, 1.628-11.983, p = 0.004). Conversion to OA was the main predictive factor of postoperative complications (OR 5.42, 1.83-16.01, p = 0.002). Under adequate supervision, the surgeon's individual experience and initial adrenal disease were not considered predictive of complications.

Conclusion: Lesion diameter over 45 mm is the determinant parameter for guidance of patients to surgeons with more extensive experience.
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http://dx.doi.org/10.1007/s00464-016-4830-0DOI Listing
July 2017

Claire Douillard, Pascal Houillier, Juerg Nussberger and Xavier Girerd in response to the correspondence by Damien Denimal entitled: "Comments on French SFE/SFHTA/AFCE Consensus on Primary aldosteronism, Part 2: Diagnosis First steps". Ann Endocrinol 2016.

Ann Endocrinol (Paris) 2016 Dec 16;77(6):676. Epub 2016 Sep 16.

Unité de prévention cardiovasculaire, pôle coeur métabolisme, groupe hospitalier universitaire Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France.

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http://dx.doi.org/10.1016/j.ando.2016.07.003DOI Listing
December 2016

SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook.

Ann Endocrinol (Paris) 2016 Jul 15;77(3):179-86. Epub 2016 Jun 15.

AP-HP, HEGP, Service de Chirurgie Digestive, Générale et Cancérologique, 75015 Paris, France; Endocrinologie, Pavillon des Ecrins, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9, France. Electronic address:

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated.
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http://dx.doi.org/10.1016/j.ando.2016.05.001DOI Listing
July 2016

SFE/SFHTA/AFCE Consensus on Primary Aldosteronism, part 2: First diagnostic steps.

Ann Endocrinol (Paris) 2016 Jul 10;77(3):192-201. Epub 2016 May 10.

Pôle cœur métabolisme, unité de prévention cardiovasculaire, groupe hospitalier universitaire Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France.

In patients with suspected primary aldosteronism (PA), the first diagnostic step, screening, must have high sensitivity and negative predictive value. The aldosterone-to-renin ratio (ARR) is used because it has higher sensitivity and lower variability than other measures (serum potassium, plasma aldosterone, urinary aldosterone). ARR is calculated from the plasma aldosterone (PA) and plasma renin activity (PRA) or direct plasma renin (DR) values. These measurements must be taken under standard conditions: in the morning, more than 2hours after awakening, in sitting position after 5 to 15minutes, with normal dietary salt intake, normal serum potassium level and without antihypertensive drugs significantly interfering with the renin-angiotensin-aldosterone system. To rule out ARR elevation due to very low renin values, ARR screening is applied only if aldosterone is>240pmol/l (90pg/ml); DR values<5mIU/l are assimilated to 5mIU/l and PRA values<0.2ng/ml/h to 0.2ng/ml/h. We propose threshold ARR values depending on the units used and a conversion factor (pg to mIU) for DR. If ARR exceeds threshold, PA should be suspected and exploration continued. If ARR is below threshold or if plasma aldosterone is<240pmol/l (90pg/ml) on two measurements, diagnosis of PA is excluded.
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http://dx.doi.org/10.1016/j.ando.2016.02.003DOI Listing
July 2016

SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis.

Ann Endocrinol (Paris) 2016 Jul 29;77(3):208-13. Epub 2016 Mar 29.

Assistance publique-Hôpitaux de Paris, hôpital Tenon, service de médecine interne, rue de la Chine, 75020 Paris, France. Electronic address:

To establish the cause of primary aldosteronism (PA), it is essential to distinguish unilateral from bilateral adrenal aldosterone secretion, as adrenalectomy improves aldosterone secretion and controls hypertension and hypokalemia only in the former. Except in the rare cases of type 1 or 3 familial hyperaldosteronism, which can be diagnosed genetically and are not candidates for surgery, lateralized aldosterone secretion is diagnosed on adrenal CT or MRI and adrenal venous sampling. Postural stimulation tests and (131)I-norcholesterol scintigraphy have poor diagnostic value and (11)C-metomidate PET is not yet available. We recommend that adrenal CT or MRI be performed in all cases of PA. Imaging may exceptionally identify adrenocortical carcinoma, for which the surgical objectives are carcinologic, and otherwise shows either normal or hyperplastic adrenals or unilateral adenoma. Imaging alone carries a risk of false positives in patients over 35 years of age (non-aldosterone-secreting adenoma) and false negatives in all patients (unilateral hyperplasia). We suggest that all candidates for surgery over 35 years of age undergo adrenal venous sampling, simultaneously in both adrenal veins, without ACTH stimulation, to confirm the unilateral form of the hypersecretion. Sampling results should be confirmed on adrenal vein cortisol assay showing a concentration at least double that found in peripheral veins. Aldosterone secretion should be considered lateralized when aldosterone/cortisol ratio on the dominant side is at least 4-fold higher than contralaterally.
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http://dx.doi.org/10.1016/j.ando.2016.01.008DOI Listing
July 2016

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options.

J Inherit Metab Dis 2016 Mar 7;39(2):273-83. Epub 2015 Dec 7.

Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.

Background: Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods: Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results: The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion: Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.
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http://dx.doi.org/10.1007/s10545-015-9904-yDOI Listing
March 2016

Diabetes insipidus.

Ann Endocrinol (Paris) 2013 Dec 25;74(5-6):496-507. Epub 2013 Nov 25.

Service d'endocrinologie et maladies métaboliques, centre hospitalier régional universitaire de Lille (CHRU de LIlle), hôpital Huriez/Inserm U 859, 1, rue Polonovski, 59000 Lille, France.

Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of dehydration, bladder distention, pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome, granulomatosis and cancer is required. The diagnosis is based on biological assessment, pituitary magnetic resonance imaging (MRI) and results of a desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years, and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to hypopituitarism, including DI in 2% of cases. Transient or permanent DI is present in 8-9% of endoscopic transphenoidal surgeries. Current advances in DI concern the etiological work-up, with in particular the identification of IgG4-related hypophysitis or many genetic abnormalities, opening the field of targeted therapies in the years to come.
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http://dx.doi.org/10.1016/j.ando.2013.10.002DOI Listing
December 2013

A Novel Mutation in CPT1A Resulting in Hepatic CPT Deficiency.

JIMD Rep 2012 31;6:7-14. Epub 2012 Jan 31.

Laboratory of Hormonology, Metabolism-Nutrition & Oncology (HMNO), Center of Biology and Pathology, CHRU Lille, 59037, Lille, France.

The present work presents a "from gene defect to clinics" pathogenesis study of a patient with a hitherto unreported mutation in the CPT1A gene. In early childhood, the patient developed a life-threatening episode (hypoketotic hypoglycemia, liver cytolysis, and hepatomegaly) evocative of a mitochondrial fatty acid oxidation disorder, and presented deficient fibroblast carnitine palmitoyltransferase 1 (CPT1) activity and homozygosity for the c.1783 C > T nucleotide substitution on exon 15 of CPT1A (p.R595W mutant). While confirming CPT1A deficiency, whole blood de novo acylcarnitine synthesis and the levels of carnitine and its esters formally linked intracellular free-carnitine depletion to intracellular carnitine esterification. Sequence alignment and modeling of wild-type and p.*R595W CPT1A proteins indicated that the Arg595 targeted by the mutated codon is phylogenetically well conversed. It contributes to a hydrogen bond network with neighboring residues Cys304 and Met593 but does not participate in the catalysis and carnitine pocket. Its replacement by tryptophan induces steric hindrance with the side chain of Ile480 located in α-helix 12, affecting protein architecture and function. This hindrance with Ile480 is also originally described with tryptophan 304 in the known mutant p.C304W CPT1A, suggesting that the mechanisms that invalidate CPT1A activity and underlie pathogenesis could be common in both the new (p.R595W) and previously described (p.C304W) mutants.
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http://dx.doi.org/10.1007/8904_2011_94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565650PMC
February 2013

Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review.

J Inherit Metab Dis 2013 Sep 30;36(5):859-68. Epub 2012 Nov 30.

Department of Neurology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris and University Pierre&Marie Curie, Paris, France.

Krabbe disease usually presents as a severe leukodystrophy in early infancy and childhood. From a series of 11 patients and 30 cases previously reported in the literature we describe the clinical, radiological, electrophysiological and genetic features of adult Krabbe disease. Patients diagnosed after the age of 16 years were included in this study. They were further divided into three groups depending on age at symptoms onset: (1) childhood onset cases (n = 7); (2) adolescence onset cases (n = 6) and adult onset cases (n = 28). Overall, 96 % of patients in the adult-onset group presented with signs of pyramidal tracts dysfunction. Spastic paraparesis or tetraparesis became prominent in all cases. A peripheral neuropathy was present in 59 % of cases and was most often demyelinating (80 %). Other clinical signs encompassed dysarthria (31 %), cerebellar ataxia (27 %), pes cavus (27 %), deep sensory signs (23 %), tongue atrophy (15 %), optic neuropathy (12 %), cognitive decline (12 %). Cerebrospinal fluid protein concentration was moderately increased in 54 % of patients. Patients in the adolescent- and childhood-onset groups had similar presentations but were more likely to display optic neuropathy (33 % and 57 %) and cerebellar ataxia (50 % and 57 %). In the adult-onset group, the disease progressed slowly over more than 10 years, but a rapid course was observed in two patients. Abnormalities of brain MRI was similar in the three groups and included high signals of cortico-spinal tracts (94 % of cases), hyper-intensities of optic radiations (89 %) and hyper-intensities or atrophy of the posterior part of the corpus callosum (60 %). No clear genotype-phenotype relationship could be demonstrated.
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http://dx.doi.org/10.1007/s10545-012-9560-4DOI Listing
September 2013

[Hypotension from endocrine origin].

Presse Med 2012 Nov 10;41(11):1137-50. Epub 2012 Sep 10.

Centre hospitalier régional universitaire de Lille, hôpital Huriez, service d'endocrinologie et maladies métaboliques, 59000 Lille, France.

Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been prepared with calcium inhibitors. Every flush with hypotension should suggest a carcinoid crisis, which is very sensitive to subcutaneous somatostatin analog. An accurate etiological diagnosis should allow treat efficiently endocrine hypotension without inducing hypertension in supine posture.
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http://dx.doi.org/10.1016/j.lpm.2012.03.023DOI Listing
November 2012