Krabbe disease, also known as globoid cell leukodystrophy, is a lysosomal function disorder that ultimately results in demyelination and dysmyelination of white matter.

The worldwide incidence of Krabbe disease has been shown to be 1 in 100 000–200 000, with 1 in 150 000 live births reported in Europe.¹,² The incidence in the South African population has not been well established.

Krabbe disease is classified as a progressive leukodystrophy with an autosomal recessive inheritance pattern. It is caused by a mutation of the galactocerebroside beta-galactosidase gene located on chromosome 14q31.²,³

Presentation is usually between 3 and 6 months of age, with death commonly occurring before the age of 2 years. The presenting features most often encountered are regression of milestones, inconsolable irritability, and agitation and feeding problems, with an inevitable need for enteric feeding in the terminal stages of the disease.²,³,⁴,⁵

The pathophysiology of Krabbe disease results from a deficiency in the production of the enzyme galactocerebrosidase, a lysosomal enzyme that forms a key component of the myelin metabolism pathway.³ This deficiency results in progressive demyelination and dysmyelination of both the peripheral and central nervous systems.⁴,⁶

The impaired galactocerebrosidase production results in accumulation of lethal levels of galactocerebroside and psychosine within macrophages, with resultant globoid cell formation.⁴,⁷ Psychosine in particular has been shown to be toxic to oligodendroglial cells, neurons and Schwann cells.¹,³

The microscopic features of Krabbe disease typically include severe neuronal destruction in the white matter of the thalami, cerebellar peduncles, corona radiata and corpus callosum.³

Computed tomography (CT) usually shows hyperdensities in the thalami, caudate nuclei, cerebellar dentate nuclei and corona radiata during the early stages of the disease.³ As the disease progresses, associated white matter atrophy manifests, making it indistinguishable from other dysmyelinating conditions in the terminal stage.³,⁶

In very young patients, T1-weighted MRI demonstrates abnormally high signal in the thalami, with a delay in the appearance of the normal high signal in the internal capsules. High T1 signal intensities are also observed in the caudate nuclei, corona radiata, dentate nuclei of the cerebellum and also within the cerebral and cerebellar white matter. In the early stages of the disease, the subcortical white matter is spared.³,⁶

The cerebellar dentate nuclei maintain their high signal on T2-weighted imaging. In addition, there are also abnormally high T2 signal intensities within the corticospinal tracts of the internal capsules, cerebral white matter and the medial medullary pyramids. These findings are highly indicative of the disease.³

Beyond the first year of the disease, white matter high T2 signal intensities are noted to involve the splenium of the corpus callosum and the deep cerebral white matter, notably in the posterior frontal and anterior parietal lobes.³

Diffusion weighted imaging (DWI) demonstrates proportionally increased diffusion with disease progression, noted uniformly throughout the white matter. MR spectroscopy, although non-specific, may show an increased lactate and decreased N-acetylaspartate (NAA).³

Optic nerve as well as other cranial nerve enlargement, however, is seldom described in association with Krabbe disease. When present, it is thought to be as a result of globoid cell accumulation within the optic and other cranial nerves in combination with an inflammatory response related to myelin breakdown.³,⁴,⁵,⁶,⁸ Jones et al. proved the presence of globoid cells within the optic nerves on histological review of one of their analysed cases.⁶

In the presence of optic nerve enlargement, the differential diagnosis will include optic nerve glioma in patients with NF-I, optic dural ectasia, granulomatous or histiocytic infiltration of the optic nerves, post-viral optic neuritis and optic nerve medulloepithelioma.⁶,⁷ Making the distinction on clinical grounds is of great importance.

Optic atrophy is one of the clinical presenting features of Krabbe disease. However, in rare cases as we report here, optic nerve enlargement may be an association. Considering the higher prevalence of NF-I, one can easily be misled by these imaging features into making the latter diagnosis.

Early awareness of neuroimaging findings in Krabbe disease together with a suggestive clinical presentation will allow timely management and genetic counseling to parents.