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.