Genetic and Metabolic Disorders of the White Matter

A genetically proven case of Pelizaeus-Merzbacher disease: Clinicoradiological clues

“…[1] The spectrum of PLP1-related disorders include the severe connatal PMD, intermediate classical PMD, which is less severe, and the milder phenotype of spastic paraplegia type 2 (SPG2). [2] Whereas the severe forms arise due to missense mutations, deletions and null mutations account for the milder variants such as SPG2. However, the most common mutations are duplications that lead to the classical intermediate form of PMD, as is the current case.…”

“…[2] PMD is a hypomyelinating leukoencephalopathy and close clinico-radiological differentials are Pelizaeus-Merzbacher-like disorder (PMLD) and Salla disease. Characteristic clinical features and radiological presence or absence of basal ganglia, cerebellum, and brainstem involvement helps in differentiating hypomyelinating disorders.…”

“…[3] PMLD is characterized by cerebellar atrophy, whereas Salla disease has characteristic N-acetylaspartate (NAA) peak on magnetic resonance (MR) spectroscopy. [24] The genetic defects in PMLD affect the gap junction alpha-12 (GJA12) and sex-determining region Y (SRY)-box 10 (SOX10) gene that are responsible for the formation of oligodendrocytes in very early stages. [5] In Salla disease, the underlying pathogenic defect is in a lysosomal transporter protein for sialic acid.…”

“…Dysmyelinating leukodystrophies such as Cockayne disease, metachromatic leukodystrophy, Krabbe disease, and Canavan disease can also present in infancy but characteristic clinical and radiological features differentiate these disorders from PMD. [2]…”