title: Neurological presentation of a congenital disorder of glycosylation CDG-Ia: implications for diagnosis and genetic counseling.
abstract: The congenital disorders of glycosylation (CDG) constitute a new group of recessively inherited metabolic disorders that are characterized biochemically by defective glycosylation of proteins. Several types have been identified. CDG-Ia, the most frequent type, is a multisystemic disorder affecting the nervous system and numerous organs including liver, kidney, heart, adipose tissue, bone, and genitalia. A phosphomannomutase (PMM) deficiency has been identified in CDG-Ia patients and numerous mutations in the PMM2 gene have been identified in patients with a PMM deficiency. We report on a French family with 3 affected sibs, with an unusual presentation of CDG-Ia, remarkable for 1) the neurological presentation of the disease, and 2) the dissociation between intermediate PMM activity in fibroblasts and a decreased PMM activity in leukocytes. This report shows that the diagnosis of CDG-Ia must be considered in patients with non-regressive early-onset encephalopathy with cerebellar atrophy, and that intermediate values of PMM activity in fibroblasts do not exclude the diagnosis of CDG-Ia.
authors.affiliation: Service de Génétique Médicale, Hôpital Charles Nicolle, 76031 Rouen Cedex, France. genetique.clinique@chu-rouen.fr
authors.forename: V
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: M
authors.initials: M
authors.lastname: Belgrand
authors.forename: S
authors.initials: S
authors.lastname: Grünewald
authors.forename: N
authors.initials: N
authors.lastname: Seta
authors.forename: J N
authors.initials: JN
authors.lastname: Dacher
authors.forename: A
authors.initials: A
authors.lastname: Hénocq
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: T
authors.initials: T
authors.lastname: Frébourg
authors.forename: P
authors.initials: P
authors.lastname: Saugier-Veber
mesh_terms: D017668:Age of Onset; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D002946:Cisterna Magna / Q000002:abnormalities; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D020546:Fourth Ventricle / Q000002:abnormalities; D005808:Genes, Recessive; D005817:Genetic Counseling; D006031:Glycosylation; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency / Q000378:metabolism*; D013132:Spinocerebellar Degenerations
chemical_list: D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase