Congenital disorder of glycosylation, a neuroradiologic case report

A 16-year-old male patient with a known congenital disorder of glycosylation, presents to the pediatrics consultation with symptoms of a stroke-like event and transitory paresis of the left arm. After an initial CT, an MRI was scheduled.

The CT showed no early or old signs of ischaemia, nor any intracranial bleeding.
The MRI confirmed no signs of recent ischaemia on the diffusion-weighted images. The CT and MRI both showed a marked hypoplasia and atrophy of the cerebellar folia, involving both hemispheres and the vermis, with enlargement of the cerebellar fissures. The cerebellar parenchyma showed marked T2- and FLAIR-hyperintensity in comparison to the cerebral parenchyma. Associated pontine atrophy was present. The cerebellar and pontine atrophy had clearly progressed in comparison to an earlier MRI of 16 years ago, at the age of 6 months. Upon looking at the first MRI, we learned that there was already clear cerebellar hypoplasia.
Secondary to the cerebellar atrophy, there was a large T2-hyperintense CSF accumulation inferior of the cerebellar vermis. There was no displacement of the cerebellar tentorium. There was no hydrocephalus or ventricle dilatation present.

Congenital disorders of glycosylation (CDG) is an autosomal recessive disorder which is caused by abnormal glycosylation of oligosaccharides, leading to a variety of symptoms and affecting multiple systems. The most common form is CDG type-Ia and is caused by a mutation of the PPM-2 gene, which encodes a cytosolic enzyme phosphomannomutase. This specific mutation was diagnosed in our case at the age of 10 months. [1]
Typically, CDG-Ia patients will demonstrate neurological involvement, with muscular hypotonia, failure to thrive and psychomotor retardation, often in the first year of life. [1]

MR-imaging typically shows a small hypoplastic cerebellum, including the vermis and both hemispheres in the neonatal period, with progressive volume loss (atrophy) upon follow-up imaging.
The distinction between cerebellar hypoplasia and cerebellar atrophy is not always clear in practice. Cerebellar hypoplasia (CH) is a congenital condition, which presents as an underdevelopment or incomplete development of the cerebellum. In CH, the cerebellar structures are not filling a normal configured posterior fossa. Cerebellar atrophy (CA) however, implies progressive volume-loss of an initial normal cerebellum. In CA, the cerebellar structures are normally formed, yet loss of folial tissue has occurred and secondary, the fissures or interfolial spaces have progressively enlarged. [2]

This case shows a clear hypoplastic cerebellum shortly after birth, on the T1-weighted images, performed at the age of 6 months. Sixteen years later, we notice a progressive atrophy of the cerebellar folia and the pons. In accordance with other studies, we can conclude that that cerebellar atrophy can be superimposed on cerebellar hypoplasia, in CDG type-1a patients. [1, 2, 3]
A case-series by Feraco et. al, found that the presence of high T2/FLAIR signal intensity in the cerebellum was a universal finding in all of their five cases and could help in the differential diagnosis of CA and CH. In our case, this was also a marked finding. [1]
In dandy-walker malformation there is an enlarged posterior fossa, with partial to complete vermian aplasia, and secondary elevated cerebellar tentorium. Malformations like this, are therefore easily excluded from the differential diagnosis.

The stroke-like event our patient presented with, is reportedly a frequent finding in CDH-1a patients, and is most likely caused by an active epileptic inhibitory process rather than real ischaemia. [4]

To summarize, we present a typical case of CDG-1a related ponto-cerebellar degeneration. A small T2-FLAIR hyperintense and hypoplastic cerebellum, often associated with superimposed pontocerebellar atrophy can be suggestive for the diagnosis of CDG.