29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype

Orphanet Journal of Rare Diseases

Delphine Héron³  Nathalie Seta^1,15  Alexis Brice⁴  Hélène Ogier^1,13  Michèle Mayer^1,10  Valérie Cormier-Daire⁹  Philippe Khau Van Kien⁵  Valérie Drouin-Garraud²  Claire de Baracé^1,14  Perrine Charles^1,16  Aurélia Jacquette³  Emmanuel Roze¹  Marion Gérard⁷  Christel Thauvin^1,11  Catherine Lenaerts⁶  Michèle Mathieu-Dramard⁸  Alice Masurel^1,11  Bénédicte Héron^1,10  Pascale De Lonlay^1,12  Cyril Mignot³  Marie-Lorraine Monin⁴ 

[1] AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département des Maladies du Système Nerveux, Paris, France;Service de Génétique, Centre Hospitalier Universitaire de Rouen, Rouen, France;Groupe de Recherche Clinique (GRC) ‘déficience intellectuelle et autisme’, UPMC Paris 06, Paris, France;Physiopathology and Treatment of Neurodegenerative Disorders, Inserm, UMR_S975, CRICM, Team Molecular Bases, and CNRS UMR 7225, Paris, France;Unité de Génétique médicale et Cytogénétique, Centre Hospitalier Universitaire de Nîmes, Nîmes, France;Service de Pédiatrie, Centre Hospitalier Universitaire d’Amiens, Amiens, France;Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, France;Service de Génétique, Centre Hospitalier Universitaire d’Amiens, Amiens, France;AP-HP, Hôpital Necker, Service de Génétique médicale, Paris, France;AP-HP, Hôpital Trousseau, Service de Neurologie pédiatrique et Maladies du développement, Paris, France;Service de Génétique, Centre Hospitalier Universitaire de Dijon, Dijon, France;AP-HP, Hôpital Necker, Université Paris Descartes, Institut Imagine, Centre de Référence des Maladies Héréditaires du Métabolisme, Paris, France;AP-HP, Hôpital Robert Debré, Service de Neurologie pédiatrique et des Maladies métaboliques, Paris, France;Service de Pédiatrie, Centre Hospitalier de Saint Brieuc, Saint Brieuc, France;AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Biochimie métabolique et cellulaire, Paris, France;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

关键词: PMM2-CDG;    Phosphomannomutase;    Adult;    Cerebellar ataxia;    Congenital disorder of glycosylation;   

Others  :  1138688
DOI  :  10.1186/s13023-014-0207-4

 received in 2014-10-10, accepted in 2014-12-02,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Monin et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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