Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

Abstract

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an adult-onset, inherited white matter disorder encompassing two previously identified clinicopathologically similar entities: pigmentary orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with spheroids (HDLS). In this chapter, we discuss how advances in our genetic understanding of the condition have further delineated three distinct clinical entities within ALSP, namely CSF1R-related ALSP, AARS2-related leukoencephalopathy (AARS2-L), and AARS (HDLS-S). We provide descriptions of the clinical, radiologic, pathologic, and pathophysiologic findings in each entity, detailing their similarities and differences, and discuss current and future treatment options where available.

Keywords: AARS; AARS2; ALSP; CSF1R; HDLS; POLD.