Congenital disorders of glycosylation (CDG) are
genetic diseases due to defects in the synthesis or the attachment of the
glycan moiety of
glycoproteins and
glycolipids. They can be divided into four groups: disorders of
protein N-glycosylation, disorders of
protein O-glycosylation, disorders of
lipid glycosylation, and disorders of other glycosylation pathways and of multiple glycosylation pathways. Of the more than 40 reported CDG, some 80% are neurological or have an important neurological component. By far the most common neurological CDG is
phosphomannomutase 2 deficiency. Isoelectrofocusing of serum
transferrin, the most widely used screening test, picks up only CDG associated with
sialic acid deficiency of N-linked
glycans. Predominant neurological signs and symptoms are psychomotor retardation,
epilepsy,
hypotonia,
hyporeflexia,
strabismus,
retinitis pigmentosa,
polyneuropathy,
myopathy, and cerebellar hypotrophy/hypoplasia. All known neurological CDG have an autosomal recessive inheritance except for IAP-CDG, an X-linked pure
mental retardation syndrome. No curative or effective treatment is available for neurological CDG. Since at least 1% of the genome is involved in glycosylation, it is likely that the large majority of CDG is yet to be discovered. In 2008, a novel nomenclature was introduced using the gene symbol followed by -CDG, e.g., CDG-Ia becomes
PMM2-CDG. CDG should be looked for in any unexplained neurological syndrome.