Congenital disorders of glycosylation (CDG)

Metabolic diseases
Pediatric diseases

General description

Congenital disorders of glycosylation (CDG) are a genetically and clinically heterogeneous group of inherited metabolic diseases caused by defects in the synthesis, processing, or attachment of glycans to proteins and lipids. The most common types involve N-glycosylation defects, with over 150 subtypes described to date, the majority inherited in an autosomal recessive pattern, though autosomal dominant and X-linked forms also exist. The most prevalent subtype is phosphomannomutase 2 deficiency (PMM2-CDG), which is associated with multisystemic manifestations due to impaired N-glycosylation.

CDG typically present in infancy or childhood with multisystemic involvement. Common clinical features include developmental delay or intellectual disability, hypotonia, failure to thrive, cerebellar abnormalities (such as ataxia), seizures, stroke-like episodes, and peripheral neuropathy. Dysmorphic features, such as inverted nipples, abnormal fat pads, and a distinctive facial appearance, are frequently observed.

References

  1. Feraco, P., et al. "The shrunken, bright cerebellum: a characteristic MRI finding in congenital disorders of glycosylation type 1a." American journal of neuroradiology 33.11 (2012): 2062-2067.

Hypoplasia and abnormal signal

Anatomical regions
  • Cerebellum
Symmetric
Bilateral
Morphology
Atrophy
T2WI
Hyperintensity
FLAIR
Hyperintensity

Brain imaging in CDG, particularly in PMM2-CDG, reveals characteristic structural abnormalities. The most consistent neuroimaging finding is cerebellar hypoplasia, which is often apparent at or shortly after birth and may progress to cerebellar atrophy over time. On MRI, the cerebellar cortex and subcortical white matter may appear hyperintense on T2-weighted and FLAIR sequences, reflecting both hypoplasia and atrophy.

Pontine hypoplasia

Anatomical regions
  • Brainstem
    Pons
Morphology
Atrophy

The brainstem, particularly the pons, may also show reduced prominence or abnormal configuration, with a diminished pontine protuberance in some cases.