Neurological presentation of a congenital disorder of glycosylation CDG-Ia: implications for diagnosis and genetic counseling

Am J Med Genet. 2001 Jun 1;101(1):46-9. doi: 10.1002/ajmg.1298.


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.

MeSH terms

  • Age of Onset
  • Cerebellum / abnormalities*
  • Child
  • Cisterna Magna / abnormalities
  • Congenital Disorders of Glycosylation / diagnosis*
  • Congenital Disorders of Glycosylation / enzymology
  • Congenital Disorders of Glycosylation / genetics
  • Female
  • Fibroblasts / enzymology
  • Fourth Ventricle / abnormalities
  • Genes, Recessive
  • Genetic Counseling
  • Glycosylation
  • Humans
  • Isoelectric Focusing
  • Male
  • Phosphotransferases (Phosphomutases) / deficiency
  • Phosphotransferases (Phosphomutases) / metabolism*
  • Spinocerebellar Degenerations


  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase