Paving the Way to Precision Nutrition Through Metabolomics

Nutrition is an interdisciplinary science that studies the interactions of nutrients with the body in relation to maintenance of health and well-being. Nutrition is highly complex due to the underlying various internal and external factors that could model it. Thus, hacking this complexity requires more holistic and network-based strategies that could unveil these dynamic system interactions at both time and space scales. The ongoing omics era with its high-throughput molecular data generation is paving the way to embrace this complexity and is deeply reshaping the whole field of nutrition. Understanding the future paths of nutrition science is of importance from both translational and clinical perspectives. Basic nutrients which might include metabolites are important in nutrition science. Moreover, metabolites are key biological communication channels and represent an appealing functional readout at the interface of different major influential factors that define health and disease. Metabolomics is the technology that enables holistic and systematic analyses of metabolites in a biological system. Hence, given its intrinsic functionality, its tight connection to metabolism and its high clinical actionability potential, metabolomics is a very appealing technology for nutrition science. The ultimate goal is to deliver a tailored and clinically relevant nutritional recommendations and interventions to achieve precision nutrition. This work intends to present an update on the applications of metabolomics to personalize nutrition in translational and clinical settings. It also discusses the current conceptual shifts that are remodeling clinical nutrition practices in this Precision Medicine era. Finally, perspectives of clinical nutrition in the ever-growing, data-driven healthcare landscape are presented

Caractéristiques cliniques et moléculaires d une cohorte de 13 patients algériens atteints de MPS I

La mucopolysaccharidose de type I (MPS I) est une maladie lysosomale de surcharge liée au déficit d'une enzyme du métabolisme des glycomanioglycanes (GAG), a-L-Iduronidase (IDUA). C'est une maladie récessive rare et grave, avec un spectre clinique hétérogène comportant des atteintes progressives viscérales et osseuses. Trois formes cliniques ont été décrites. La forme sévère est caractérisée par un début de signes précoce et un retard intellectuel. Dans les formes atténuées, les symptômes surviennent plus tardivement et l'atteinte neurologique est absente ou modérée. Nous rapportons pour la première fois, une étude descriptive portant sur 13 patients algériens atteints de MPS I. Le séquençage du gène IDUA a été réalisé dans le cadre de cette étude. Notre cohorte comporte majoritairement des patients de phénotype atténué (12/13). Chez ces patients, la dysmorphie faciale, la valvulopathie, l'opacité cornéenne et la présence de hernie ombilicale sont quasi systématiques. Les données biochimiques trouvent chez tous les sujets une excrétion accrue de GAG, et les profils qualitatifs montrent la présence de bandes de dermatane et héparane sulfate. L'activité enzymatique IDUA est effondrée chez tous les patients. L'analyse moléculaire a mis en évidence 4 variations pathologiques déjà connues, les mutations faux-sens p.P533R (C.1598C>G) et p.E178K (C.532G>A), et les mutations non-sens p.Y167X (C.501C>G) et p.Y581X (C.1743C>G). La mutation p.P533R est prédominante, elle est retrouvée dans 84% des cas. Une meilleure caractérisation des patients atteints de MPS I contribue à définir l'histoire naturelle de la maladie et à la compréhension de ses bases physiopathologiques.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease

Aims A hallmark of Fabry disease is the concomitant development of left-ventricular hypertrophy and arterial intima-media thickening, the pathogenesis of which is thought to be related to the presence of a plasmatic circulating growth-promoting factor. We therefore characterized the plasma of patients with Fabry disease in order to identify this factor. Methods and results Using a classical biochemical strategy, we isolated and identified sphingosine-1 phosphate (S1P) as a proliferative factor present in the plasma of patients with Fabry disease. Plasma S1P levels were significantly higher in 17 patients with Fabry disease compared with 17 healthy controls (225 ± 40 vs. 164 ± 17 ng/mL; P = 0.005). There was a positive correlation between plasma S1P levels and both common carotid artery intima-media thickness and left-ventricular mass index (r2 = 0.47; P = 0.006 and r2 = 0.53; P = 0.0007, respectively). In an experimental model, mice treated with S1P developed cardiovascular remodelling similar to that observed in patients with Fabry disease. Conclusion Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry diseas

Plasma carnitine is associated with fatigue in chronic hepatitis C but not in irritable bowel syndrome : Carnitine and fatigue in hepatitis C

International audienceObjectives Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C (CHC) or the irritable bowel syndrome (IBS). In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in CHC and IBS. Methods We enrolled 70 patients with CHC, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured. Results Fatigue scores were significantly more elevated in patients with CHC and IBS than in healthy subjects. Patients with CHC, but not with IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared to healthy subjects. In patients with CHC, and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with CHC (OR=2.019, p=0.02, CI 95% [1.01-1.23]).Conclusions In patients with CHC, the severity of fatigue is associated with low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in CHC. The underlying mechanism of fatigue in IBS does not seem to involve carnitine

Etude moléculaire de la cystinurie dans une population franco-suisse

La cystinurie est une aminoacidurie de transmission autosomique récessive. Cette pathologie se caractérise par un défaut de réabsorption des acides aminés dibasiques au niveau de l'anse de Henle et se traduit par la formation de lithiases rénales de cystine. L'altération du transporteur des acides aminés dibasiques, nommée b 0,+, consécutive à des mutations des gènes SLC3A1 et/ou SLC7A9 est à l'origine de cette maladie. L'étude moléculaire de ces gènes est réalisée au CHU de Rouen dans le cadre du Programme National de Soutien au Diagnostic Génétique des Maladies Rares. Une étude multicentrique a permis l'étude de 124 patients dont 93 cas index. La recherche de mutations a été effectuée par séquençage direct des gènes SLC3A1 et SLC7A9. De plus, pour caractériser les grands remaniements ou des délétions hétérozygotes, une technique de PCR quantitative par QMPSF du gène SLC3A1 a été mise au point et réalisée dans le cadre de cette thèse. L'étude a permis le diagnostic moléculaire de 81 sur 93 patients établissant ainsi la première description des causes génétiques de la cystinurie d'une population franco-suisse. Il a été mis en évidence une proportion importante du génotype A (67,7 %). Le diagnostic moléculaire a été réalisé et complété dans 87,1 % des cas. La mise en place de la QMPSF du gène SLC7A9 et la finalisation d'études d'épissage de certaines mutations permettront d'améliorer ce résultat. L'absence de génotype AB chez les cas index de cette étude et l'existence de ce génotype chez des apparentés asymptomatiques renforcent l'hypothèse de la non existence de cystinurie de type AB. Au final, il semble nécessaire que le diagnostic moléculaire de la cystinurie inclus des techniques permettant la recherche de grands remaniements. De plus, des investigations supplémentaires doivent être entreprises chez tout patient présentant un génotype AB afin de s'affranchir de l'existence d'une troisième mutation.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

X-Linked Sideroblastic Anemia and Ataxia – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE. CLINICAL CHARACTERISTICS: X-linked sideroblastic anemia and ataxia (XLSA/A) is characterized by moderate anemia and early-onset spinocerebellar syndrome in males, manifest primarily as delayed walking, ataxia evident in early childhood, dysmetria, and dysdiadochokinesis. When present the intention tremor is mild and the dysarthria is mild to moderately severe. The ataxia has been described to be either non-progressive or slowly progressive. Upper motor neuron (UMN) signs in the legs, manifest by brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses, are present in some males. Need for crutches or a wheelchair has been reported. Strabismus is seen in some males. Nystagmus and hypometric saccades may occur. Mild learning disability and depression are seen. The moderate hypochromic and microcytic anemia does not cause symptoms. Carrier (heterozygous) females have a normal neurologic examination and may show mild hematologic abnormalities. DIAGNOSIS/TESTING: The diagnosis of XLSA/A is suspected in males with characteristic neurologic findings and the presence of moderate hypochromic and microcytic anemia, elevated whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP), and ring sideroblasts on bone marrow examination. Pappenheimer bodies are seen in peripheral blood smear. The diagnosis is confirmed in a male by identification of a hemizygous pathogenic variant in ABCB7. Females have a normal neurologic examination and may have a dimorphic blood smear with both hypochromic microcytic red blood cells and normal red blood cells; they may have ring sideroblasts on bone marrow examination. MANAGEMENT: Treatment of manifestations: Males with XLSA/A benefit from early physical therapy to facilitate acquisition of gross motor skills. Adaptive devices such as ankle fixation orthoses and walkers may be needed. Weighted eating utensils may help promote independent skills in childhood. Speech therapy may improve intelligibility problems from dysarthria. Difficulty with handwriting may be managed with computers for word processing. GENETIC COUNSELING: XLSA/A is inherited in an X-linked manner. Heterozygous females have a 50% chance of transmitting the pathogenic variant in each pregnancy. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be affected. Males with XLSA/A will pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing of at-risk female relatives and prenatal testing for a pregnancy at increased risk are possible if the ABCB7 pathogenic variant in the family is known.status: publishe

Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

International audienc

Intraventricular Hemorrhage in Very Preterm Infants: A Comprehensive Review

Germinal matrix-intraventricular-intraparenchymal hemorrhage (GMH-IVH-IPH) is a major complication of very preterm births before 32 weeks of gestation (WG). Despite progress in clinical management, its incidence remains high before 27 WG. In addition, severe complications may occur such as post-hemorrhagic hydrocephalus and/or periventricular intraparenchymal hemorrhage. IVH is strongly associated with subsequent neurodevelopmental disabilities. For this review, an automated literature search and a clustering approach were applied to allow efficient filtering as well as topic clusters identification. We used a programmatic literature search for research articles related to intraventricular hemorrhage in preterms that were published between January 1990 and February 2020. Two queries ((Intraventricular hemorrhage) AND (preterm)) were used in PubMed. This search resulted in 1093 articles. The data manual curation left 368 documents that formed 12 clusters. The presentation and discussion of the clusters provide a comprehensive overview of existing data on the pathogenesis, complications, neuroprotection and biomarkers of GMH-IVH-IPH in very preterm infants. Clinicians should consider that the GMH-IVH-IPH pathogenesis is mainly due to developmental immaturity of the germinal matrix and cerebral autoregulation impairment. New multiomics investigations of intraventricular hemorrhage could foster the development of predictive biomarkers for the benefit of very preterm newborns

Precision Neurosurgery: A Path Forward

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology

A Case of Type I Sialidosis With Osteonecrosis Revealing a New Mutation in

Sialidosis is a rare lysosomal storage disease. The 2 forms described are as follows: the early-onset form, or type II, presents with dysostosis multiplex, while the late-onset form, or type I, does not involve bone in the literature. We report the case of a 42-year-old woman with type I sialidosis who presents with osteonecrosis of both humeral and femoral heads. Molecular study reveals a never listed mutation of NEU1 in exon 5, p.Gly273Asp (c.818G>A), and a second known missense mutation