Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature.

Autor:	Schiff M; Reference Center for Inherited Metabolic Diseases, AP-HP, Robert Debré Hospital, University Paris Diderot-Sorbonne Paris Cité, Paris, France.; INSERM U1141, Paris, France., Roda C; Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France., Monin ML; Department of Genetics, Molecular and Cellular Neurogenetics Unit, Reference Center for Intellectual of Rare Causes, AP-HP, GH Pitié-Salpêtrière, Paris, France., Arion A; Department of Paediatrics, Paediatric Care Unit, Caen Hospital, Caen, France., Barth M; Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France.; UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France., Bednarek N; Neonatal Intensive Care Unit, Institute of Alix de Champagne, Reims University Hospital, Reims, France., Bidet M; Department of Paediatric Endocrinology, Gynaecology, and Diabetology, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, Paris, France., Bloch C; Paediatric Unit, Fondation Lenval, Nice, France., Boddaert N; Department of Paediatric Radiology, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, Paris, France.; Sorbonne Paris Cité, INSERM U1000, Paris, France.; UMR 1163, Paris, France., Borgel D; Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France.; UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France., Brassier A; Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France., Brice A; Sorbonne Universités, UPMC Univ Paris 06, UMR S1127, Paris, France.; INSERM U1127, Paris, France.; CNRS UMR7225, Paris, France.; Brain and Spine Institute (ICM), Paris, France., Bruneel A; Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France., Buissonnière R; Pediatric Unit, André Mignot Hospital, Versailles, France., Chabrol B; Reference Center for Inherited Metabolic Diseases, Timone Enfants University Hospital, Marseille, France., Chevalier MC; Department of Paediatrics, Le Mans Hospital, Le Mans, France., Cormier-Daire V; Departement of Genetics, Centre of Reference for Skeletal Dysplas, AP-HP, Necker-Enfants Malades Hospital, Paris, France.; INSERM UMR1163, IMAGINE Institute affiliate, Paris, France.; University Paris Descartes-Sorbonne Paris Cité, Paris, France., De Barace C; Paediatric Unit, Saint Brieuc Hospital, Saint Brieuc, France., De Maistre E; Haematological Laboratory, Dijon Hospita, Dijon, France., De Saint-Martin A; Paediatric Neurology, Department of Pediatrics, University Hospital, Strasbourg, France., Dorison N; Pediatric Neurology Department and Neurofibromatosis Reference Center, AP-HP, Armand Trousseau Hospital, Paris, France., Drouin-Garraud V; Medical Genetics Unit, Rouen University Hospital, Rouen, France., Dupré T, Echenne B; Paediatric Neurology Unit, University of Montpellier I, Montpellier, France., Edery P; Department of Genetic, Lyon University Hospitals, Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon, France., Feillet F; Faculty of Medicine of Nancy, INSERM U954, NGERE-Nutrition, Genetics, and Environmental Risk Exposure, University of Lorraine, Vandoeuvre-lès-Nancy, France., Fontan I; Department of Dermatology and Paediatric Dermatology, Bordeaux University Hospitals, Bordeaux, France., Francannet C; Medical Genetics Unit, Clermont-Ferrand Hospital, Clermont-Ferrand, France., Labarthe F; Department of Paediatric, Tours Regional University Hospitals, Tours, France., Gitiaux C; Department of Child Neurology, Reference Centre for Neuromuscular Diseases, AP-HP, Necker-Enfants Malades Hospital, Paris, France., Héron D; GRC Intellectual Disability and Autism, UPMC Univ Paris 6, Paris, France., Hully M; Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France., Lamoureux S; Department of Paediatric, Henri-Duffaut Hospital, Avignon, France., Martin-Coignard D; Department of Genetic, Le Mans Hospital, Le Mans, France., Mignot C; Department of Genetics, Molecular and Cellular Neurogenetics Unit, Reference Center for Intellectual of Rare Causes, AP-HP, GH Pitié-Salpêtrière, Paris, France., Morin G; Department of Genetic, Amiens University Hospital, Amiens, France., Pascreau T; Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France.; UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France., Pincemaille O; Department of Paediatrics, Grasse Hospital, France., Polak M; Department of Paediatric Endocrinology, Gynaecology, and Diabetology, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, Paris, France., Roubertie A, Thauvin-Robinet C; Departement of Genetic, Children's Hospital, Dijon, France., Toutain A; Division of Genetics, Bretonneau Hospital, Tours, France., Viot G; Department of Gynecology-Obstetrics, Faculty of Medicine, AP-HP, Cochin Hospital, Paris Descartes University‒Sorbonne Paris Cité, Paris, France., Vuillaumier-Barrot S; Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France., Seta N; Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France., De Lonlay P; Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2017 Dec; Vol. 54 (12), pp. 843-851. Date of Electronic Publication: 2017 Sep 27.
DOI:	10.1136/jmedgenet-2017-104903
Abstrakt:	Background: Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a multisystem inborn error of metabolism. Objectives: To better characterise the natural history of PMM2-CDG. Methods: Medical charts of 96 patients with PMM2-CDG (86 families, 41 males, 55 females) were retrospectively reviewed. Data on clinical, laboratory and molecular parameters at diagnosis were analysed. Follow-up data at last examination were reported for 25 patients. Results: The patients were born between 1963 and 2011. Diagnosis of PMM2-CDG was made at a mean (SD) age of 6.8 (8.5) years. The presenting signs were mostly neurological (hypotonia, intellectual disability, cerebellar syndrome) and observed in almost all the patients. A total of 38 patients (14 males, 24 females) exhibited, in addition to neurological signs, visceral features including at least one of these: feeding difficulty requiring a nutritional support (n=23), cardiac features (n=20; pericarditis: 14, cardiac malformation: 9, cardiomyopathy: 2), hepato-gastrointestinal features (n=12; chronic diarrhoea: 7, protein-losing enteropathy: 1, ascites: 3, liver failure: 1, portal hypertension: 1), kidney features (n=4; nephrotic syndrome: 2, tubulopathy: 2) and hydrops fetalis (n=1). Twelve patients died at a mean age of 3.8 years (especially from pericarditis and other cardiac issues). Laboratory abnormalities mostly included elevated transaminases and abnormal coagulation parameters. High thyreostimulin levels, hypocholesterolemia, hypoalbuminemia and elevated transaminases were associated with the visceral phenotype. Besides the common Arg141His PMM2 variant harboured by half of the patients, 45 different variants were observed. Conclusions: PMM2-CDG clinical phenotype is heterogeneous in terms of clinical course, with no clear division between neurological and visceral presentations. Competing Interests: Competing interests: None declared. (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Databáze:	MEDLINE
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