General description

Pelizaeus-Merzbacher disease (PMD), also known as hypomyelinating leukodystrophy 1 (HLD1), is an X-linked recessive hereditary demyelinating disorder caused primarily by abnormalities in the proteolipid protein 1 (PLP1) gene, which is essential for myelin formation in the central nervous system. This disease affects only males and is typically noticed in early infancy due to symptoms such as nystagmus. Other clinical features include head tremors, delayed psychomotor development, hypotonia, and additional complications such as cerebellar symptoms (ataxia, tremors), basal ganglia symptoms (rigidity, dystonia), and spastic seizures. Over time, muscle tone and tendon reflexes become hyperactive, while nystagmus becomes less prominent.

PMD is classified into two main types: connatal and classic. The connatal type is more severe, with symptoms present at birth or in the neonatal period, leading to significant motor impairment, including an inability to support the head, and often resulting in death in infancy. The classic type has a later onset, with delayed but eventual acquisition of head control, and patients may survive into adulthood (20–60 years). Although motor development is severely impaired, intellectual abilities are relatively preserved.

While most PMD cases are associated with PLP1 gene abnormalities, a small proportion of patients do not have identifiable mutations in this gene, suggesting the involvement of other genetic factors in the disease.

MR spectroscopy

N-acetylaspartate (NAA), which typically decreases in many neurological diseases, remains normal or even elevated. Additionally, choline (Cho), a marker of myelination, is reduced, reflecting dysmyelination. These characteristics help in the diagnostic process.