Cysts in White Matter: A Novel Neuroimaging Finding in Infantile GM1 Gangliosidosis.

Neuroimaging, though not diagnostic, plays an important role in the evaluation of children with developmental delay/regression of milestones. It guides in ordering further diagnostic tests such as specific enzyme assays and gene panel testing. GM1 gangliosidosis is a rare autosomal-recessive disorder that is caused by deficiency of β-galactosidase enzyme. Diffuse white matter signal changes are usually seen on the magnetic resonance imaging (MRI). The basal ganglia and thalamus display subtle signal changes on MRI, with a slightly increased or decreased signal intensity of the thalamus and a slightly increased signal intensity of the basal ganglia on T2-weighted (T2W) images and a variably increased signal intensity of the thalamus on T1-weighted images.[1] Cysts in the white matter in GM1 gangliosidosis have not been reported earlier.[2]

A 15-month-old boy, born to parents who share an uncle-niece relationship, presented with complaints of developmental delay, poor vision, large head, irritability, and noisy breathing. Examination revealed macrocephaly (Head circumference-47 cm), coarse facies, alveolar hypertrophy, and hepatosplenomegaly. The cornea and fundus examination was normal. MRI showed ventriculomegaly with white matter hyperintensities in the periventricular white matter. The thalami showed hyperintense signal change on T1 and hypointensities on T2W images. The white matter in the frontal lobes showed cystic changes bilaterally [Figure 1]. Lysosomal enzyme assay in cultured skin fibroblasts revealed galactosidase activity of 0.38 nmol/mg/h (normal range: 248-24 nmol/mg/h). Genetic testing by next-generation sequencing showed homozygous mutation in GLB gene thereby confirming diagnosis of GM1 gangliosidosis.

Figure 1

Axial T1W (a and b), T2-weighted (c and d) and FLAIR (e and f) magnetic resonance images showing cysts in the frontal white matter (Horizontal arrows). T2-weighted and FLAIR images show bilateral periventricular white matter hyperintensities and thalamic hypointensities (c-f) whereas the thalami are hyperintense on T1W images (a and b) (Vertical arrows)

In Type 1, GM1 gangliosidosis-computed tomography of the brain typically shows a slightly increased density of the thalamus.[3] There is severely delayed and disturbed myelination in GM1 gangliosidosis resulting in the diffuse white matter hyperintensities on MRI. White matter gliosis and some myelin destruction add to the signal changes which are seen on neuroimaging. Severe destruction of the white matter can result in cysts in the white matter. The basal ganglia and thalamus display subtle signal changes on MRI, with a slightly increased or decreased signal intensity of the thalamus and a slightly increased signal intensity of the basal ganglia on T2W images and a variably increased signal intensity of the thalamus on T1-weighted images.[4]

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