Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity?

Area of Science:

• Neurology
• Neuroscience
• Genetics

Background:

• Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD) are considered distinct adult-onset neurodegenerative diseases.
• Both conditions manifest with dementia, motor deficits, and epilepsy.

Purpose of the Study:

• To review existing literature and evaluate the evidence supporting the unification of HDLS and POLD into a single disease entity.
• To propose a new collective classification for these related leukoencephalopathies.

Main Methods:

• Comprehensive literature review of studies on HDLS and POLD.
• Comparative analysis of clinical presentations, pathological hallmarks, and genetic data.

Main Results:

• Familial POLD shares significant clinical similarities with HDLS, including dementia, motor impairment, and epilepsy.
• Pathological findings, such as axonal spheroids (HDLS) and pigmented macrophages (POLD), are present in both conditions.
• Slight differences in age of onset, disease progression, and neurological involvement were noted but do not warrant separate classification.

Conclusions:

• HDLS and POLD represent a single disease entity, not distinct conditions.
• The collective term adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is proposed to encompass both previously separate diagnoses.
• This reclassification aids in understanding and potentially treating these rare neurological disorders.