title: 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.
abstract: PMM2-CDG (formerly known as CDG Ia) a deficiency in phosphomannomutase, is the most frequent congenital disorder of glycosylation. The phenotype encompasses a wide range of neurological and non-neurological manifestations comprising cerebellar atrophy and intellectual deficiency. The phenotype of the disorder is well characterized in children but the long term course of the disease is unknown and the phenotype of late onset forms has not been comprehensively described. We thus retrospectively collected the clinical, biological and radiological data of 29 French PMM2-CDG patients aged 15 years or more with a proven molecular diagnosis (16 females and 13 males). In addition, thirteen of these patients were reexamined at the time of the study to obtain detailed information. 27 of the 29 patients had a typical PMM2-CDG phenotype, with infantile hypotonia, strabismus, developmental delay followed by intellectual deficiency, epilepsy, retinitis pigmentosa and/or visceral manifestations. The main health problems for these patients as teenagers and in adulthood were primary ovarian insufficiency, growth retardation, coagulation anomalies and thrombotic events, skeletal deformities and osteopenia/osteoporosis, retinitis pigmentosa, as well as peripheral neuropathy. Three patients had never walked and three lost their ability to walk. The two remaining patients had a late-onset phenotype unreported to date. All patients (n = 29) had stable cerebellar atrophy. Our findings are in line with those of previous adult PMM2-CDG cohorts and points to the need for a multidisciplinary approach to the follow up of PMM2-CDG patients to prevent late complications. Additionally, our findings add weight to the view that PMM2-CDG may be diagnosed in teenage/adult patients with cerebellar atrophy, even in the absence of intellectual deficiency or non-neurological involvement.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Monin
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.forename: Pascale
authors.initials: P
authors.lastname: De Lonlay
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel
authors.forename: Michèle
authors.initials: M
authors.lastname: Mathieu-Dramard
authors.forename: Catherine
authors.initials: C
authors.lastname: Lenaerts
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin
authors.forename: Marion
authors.initials: M
authors.lastname: Gérard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
authors.forename: Aurélia
authors.initials: A
authors.lastname: Jacquette
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.forename: Claire
authors.initials: C
authors.lastname: de Baracé
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Michèle
authors.initials: M
authors.lastname: Mayer
authors.forename: Hélène
authors.initials: H
authors.lastname: Ogier
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Nathalie
authors.initials: N
authors.lastname: Seta
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique, Unité Fonctionnelle de Neurogénétique moléculaire et cellulaire et Centre de Référence des Déficiences Intellectuelles de Causes Rares, 47-83 boulevard de l'hôpital, Paris, 75013, France. delphine.heron@psl.aphp.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Héron
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015331:Cohort Studies; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency* / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human