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PMID: 28954837 Published · ppublish English Case Reports Journal Article Review Research Support, Non-U.S. Gov't

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.

Journal of medical genetics ·Vol. 54 ·No. 12 ·2017-00-00 ·Pages 843-851

Schiff M, Roda C, Monin ML, Arion A, Barth M, Bednarek N, Bidet M, Bloch C, Boddaert N, Borgel D, Brassier A, Brice A, Bruneel A, Buissonnière R, Chabrol B, Chevalier MC, Cormier-Daire V, De Barace C, De Maistre E, De Saint-Martin A, Dorison N, Drouin-Garraud V, Dupré T, Echenne B, Edery P, Feillet F, Fontan I, Francannet C, Labarthe F, Gitiaux C, Héron D, Hully M, Lamoureux S, Martin-Coignard D, Mignot C, Morin G, Pascreau T, Pincemaille O, Polak M, Roubertie A, Thauvin-Robinet C, Toutain A, Viot G, Vuillaumier-Barrot S, Seta N, De Lonlay P

Abstract

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a multisystem inborn error of metabolism. To better characterise the natural history of PMM2-CDG. 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. 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. PMM2-CDG clinical phenotype is heterogeneous in terms of clinical course, with no clear division between neurological and visceral presentations.

Keywords

CDG-I PMM2-CDG congenital disorders of glycosylation phosphomannomutase

MeSH Terms

Adolescent Alleles Amino Acid Substitution Child Child, Preschool Congenital Disorders of Glycosylation/diagnosis,genetics,mortality Female Follow-Up Studies Genetic Association Studies Humans Infant Male Mutation Phenotype Phosphotransferases (Phosphomutases)/genetics,metabolism

Chemicals

Phosphotransferases (Phosphomutases) phosphomannomutase 2, human

Authors & Affiliations

46 authors, click to expand affiliations / ORCID

Schiff Manuel ORCID

Reference Center for Inherited Metabolic Diseases, AP-HP, Robert Debré Hospital, University Paris Diderot-Sorbonne Paris Cité, Paris, France. | INSERM U1141, Paris, France.

Roda Céline

Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France.

Monin Marie-Lorraine

Department of Genetics, Molecular and Cellular Neurogenetics Unit, Reference Center for Intellectual of Rare Causes, AP-HP, GH Pitié-Salpêtrière, Paris, France.

Arion Alina

Department of Paediatrics, Paediatric Care Unit, Caen Hospital, Caen, France.

Barth Magali

Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France. | UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France.

Bednarek Nathalie

Neonatal Intensive Care Unit, Institute of Alix de Champagne, Reims University Hospital, Reims, France.

Bidet Maud

Department of Paediatric Endocrinology, Gynaecology, and Diabetology, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, Paris, France.

Bloch Catherine

Paediatric Unit, Fondation Lenval, Nice, France.

Boddaert Nathalie

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 Delphine

Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France. | UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France.

Brassier Anaïs

Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France.

Brice Alexis

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 Arnaud

Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France.

Buissonnière Roger

Pediatric Unit, André Mignot Hospital, Versailles, France.

Chabrol Brigitte

Reference Center for Inherited Metabolic Diseases, Timone Enfants University Hospital, Marseille, France.

Chevalier Marie-Chantal

Department of Paediatrics, Le Mans Hospital, Le Mans, France.

Cormier-Daire Valérie

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 Claire

Paediatric Unit, Saint Brieuc Hospital, Saint Brieuc, France.

De Maistre Emmanuel

Haematological Laboratory, Dijon Hospita, Dijon, France.

De Saint-Martin Anne

Paediatric Neurology, Department of Pediatrics, University Hospital, Strasbourg, France.

Dorison Nathalie

Pediatric Neurology Department and Neurofibromatosis Reference Center, AP-HP, Armand Trousseau Hospital, Paris, France.

Drouin-Garraud Valérie

Medical Genetics Unit, Rouen University Hospital, Rouen, France.

Dupré Thierry

Echenne Bernard

Paediatric Neurology Unit, University of Montpellier I, Montpellier, France.

Edery Patrick

Department of Genetic, Lyon University Hospitals, Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon, France.

Feillet François

Faculty of Medicine of Nancy, INSERM U954, NGERE-Nutrition, Genetics, and Environmental Risk Exposure, University of Lorraine, Vandoeuvre-lès-Nancy, France.

Fontan Isabelle

Department of Dermatology and Paediatric Dermatology, Bordeaux University Hospitals, Bordeaux, France.

Francannet Christine

Medical Genetics Unit, Clermont-Ferrand Hospital, Clermont-Ferrand, France.

Labarthe François

Department of Paediatric, Tours Regional University Hospitals, Tours, France.

Gitiaux Cyril

Department of Child Neurology, Reference Centre for Neuromuscular Diseases, AP-HP, Necker-Enfants Malades Hospital, Paris, France.

Héron Delphine

GRC Intellectual Disability and Autism, UPMC Univ Paris 6, Paris, France.

Hully Marie

Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France.

Lamoureux Sylvie

Department of Paediatric, Henri-Duffaut Hospital, Avignon, France.

Martin-Coignard Dominique

Department of Genetic, Le Mans Hospital, Le Mans, France.

Mignot Cyril

Department of Genetics, Molecular and Cellular Neurogenetics Unit, Reference Center for Intellectual of Rare Causes, AP-HP, GH Pitié-Salpêtrière, Paris, France.

Morin Gilles

Department of Genetic, Amiens University Hospital, Amiens, France.

Pascreau Tiffany

Hematology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France. | UMR INSERM 1176, Le Kremlin-Bicêtre, Paris, France.

Pincemaille Olivier

Department of Paediatrics, Grasse Hospital, France.

Polak Michel

Department of Paediatric Endocrinology, Gynaecology, and Diabetology, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, Paris, France.

Roubertie Agathe

Thauvin-Robinet Christel

Departement of Genetic, Children's Hospital, Dijon, France.

Toutain Annick

Division of Genetics, Bretonneau Hospital, Tours, France.

Viot Géraldine

Department of Gynecology-Obstetrics, Faculty of Medicine, AP-HP, Cochin Hospital, Paris Descartes University‒Sorbonne Paris Cité, Paris, France.

Vuillaumier-Barrot Sandrine

Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France.

Seta Nathalie

Department of Biochemistry, AP-HP, Bichat Hospital, Rouen, France.

De Lonlay Pascale

Reference Center for Inherited Metabolic Disease, AP-HP, Necker-Enfants Malades Hospital, IMAGINE Institute affiliate, University Paris Descartes-Sorbonne Paris Cité, Paris, France.

Conflict of Interest

Competing interests: None declared.

Article Info

Journal

Journal of medical genetics

Abbr.

J Med Genet

ISSN

1468-6244

DOI

10.1136/jmedgenet-2017-104903

Published

2017-00-00

Epub

2017-00-27

Pages

843-851

Language

English

Region

England

NLM ID

2985087R

Subset

External Links

PubMed source DOI: 10.1136/jmedgenet-2017-104903 View journal details

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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.

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