Hereditary diffuse leukoencephalopathy with spheroids

Adult-onset Leukoencephalopathy with axonal spheroids and pigmented glia (ALSP); HDLS; CSFR1 related leukodystrophy

Inheritance:

Autosomal dominant

Inheritance from one parent will result in the disease

Age range at onset:

Usually 40+ but wide range from 18 to 70s

Specialists you may see:

Geneticist

Symptoms

Personality changes are a common and early symptom of HDLS, including depression, anxiety and loss of social inhibitions. Memory loss and the loss of ability to plan and implement actions will follow. Mild seizures may occur early in the disease progression.

Walking difficulties become apparent as the condition progresses, with movement issues developing to include bradykinesia, tremors and rigidity. Eventually the affected individual becomes unable to walk, talk or care for themselves.

Cause

Caused by mutations in the CSF1R gene. This gene provides instructions to make the CSF-1 receptor protein which stimulates signalling pathways needed for cell growth, division and differentiation. Mutations prevent these signalling pathways from being stimulated, but it is not clear how this leads to white matter damage and cognitive difficulties.

This condition is clinically, radiologically and pathologically similar to AARS2-related leukodystrophy, caused by mutations in the AARS2 gene.