Early Radiologic Pattern in a Patient with Megaloencephalic Leukoencephalopathy Due to Homozygous MLC1 Mutation

Background/Purpose: Megaloencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare autosomal recessive disease caused by mutations in the MLC1 or GLIALCAM genes. MLC is characterized by infantile-onset macrocephaly and diffuse white matter involvement with subcortical cysts. Depending on the genetic background, motor deterioration with ataxia and spasticity, cognitive decline, and seizures occur. We aim to illustrate clinical features and MRI findings in a very early stage of MLC.

Methods: Our patient is a 8-month-old boy who was born at term with a head circumference at the 90th percentile (37 cm). He is the second, male child of non-consanguineous Serbian parents and was referred to our outpatient clinic with rapidly progressive macrocephaly (53 cm, 5.8 cm above 97th percentile), mild gross motor developmental delay, and generalized muscular hypotonia.

Results: cMRI revealed severe infra- and supratentorial white matter pathologies involving U-fibers. T2-weighted images showed areas of increased hyperintensity at the centra semiovale and one small cyst in the left frontal lobe. MR spectroscopy and metabolic investigations were normal. Molecular analysis revealed a homozygous MLC1 mutation in exon 8 c.[594_597del];[594_597del] p.[(Tyr198*)];[(Tyr198*).

Conclusion: In MLC, subcortical cysts can be almost invariably detected especially in the anterior temporal region. In the early stage of MLC-associated leukoencephalopathy, this characteristic finding can be very discrete, as our patient demonstrates. After exclusion of other megaloencephalic leukoencephalopathies as Canavan disease or Glutaric aciduria type I by radiologic findings, specific acylcarnitine and organic acid profiles, genetic testing of the MLC genes should be undertaken even in absence of clear subcortical cysts.