TY - JOUR T1 - 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 JF - Journal of Medical Genetics JO - J Med Genet SP - 843 LP - 851 DO - 10.1136/jmedgenet-2017-104903 VL - 54 IS - 12 AU - Manuel Schiff AU - Céline Roda AU - Marie-Lorraine Monin AU - Alina Arion AU - Magali Barth AU - Nathalie Bednarek AU - Maud Bidet AU - Catherine Bloch AU - Nathalie Boddaert AU - Delphine Borgel AU - Anaïs Brassier AU - Alexis Brice AU - Arnaud Bruneel AU - Roger Buissonnière AU - Brigitte Chabrol AU - Marie-Chantal Chevalier AU - Valérie Cormier-Daire AU - Claire De Barace AU - Emmanuel De Maistre AU - Anne De Saint-Martin AU - Nathalie Dorison AU - Valérie Drouin-Garraud AU - Thierry Dupré AU - Bernard Echenne AU - Patrick Edery AU - François Feillet AU - Isabelle Fontan AU - Christine Francannet AU - François Labarthe AU - Cyril Gitiaux AU - Delphine Héron AU - Marie Hully AU - Sylvie Lamoureux AU - Dominique Martin-Coignard AU - Cyril Mignot AU - Gilles Morin AU - Tiffany Pascreau AU - Olivier Pincemaille AU - Michel Polak AU - Agathe Roubertie AU - Christel Thauvin-Robinet AU - Annick Toutain AU - Géraldine Viot AU - Sandrine Vuillaumier-Barrot AU - Nathalie Seta AU - Pascale De Lonlay Y1 - 2017/12/01 UR - http://jmg.bmj.com/content/54/12/843.abstract N2 - 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. ER -