Magnetic resonance imaging and spectroscopy in hypomyelinating leukodystrophy

Recent advancements in molecular biology and radiology have led to the identification of several new leukodystrophies. A key diagnostic feature of leukodystrophies is the increased white matter signal intensity observed on T2-weighted magnetic resonance (MR) images. Leukodystrophies are typically classified into two main categories: hypomyelinating leukodystrophies (HLD) and other forms, including demyelinating leukodystrophies. HLD is characterized by a primary defect in myelin due to genetic variants that affect structural myelin proteins, oligodendrocyte transcription factors, RNA translation, and lysosomal proteins. Radiologically, HLD tends to show less pronounced white matter hyperintensity on T2-weighted images than demyelinating leukodystrophies. A definitive diagnosis can often be made by identifying abnormalities in regions beyond the white matter, such as the basal ganglia or cerebellum, or through the presence of characteristic clinical symptoms. N-acetylaspartate, a neuroaxonal marker observed on MR spectroscopy, is typically reduced in many neurological conditions, but N-acetylaspartate levels often remain normal in HLD, which is considered a distinctive feature of this disorder. This article provides an overview of the latest imaging findings and clinical features associated with HLD.