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Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
2012 Aug 30 [updated 2014 Dec 18].



Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), which includes both hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), is characterized by executive dysfunction, memory decline, personality changes, motor impairments, and seizures. A frontal lobe syndrome (e.g., loss of judgment, lack of social inhibitors, lack of insight, and motor persistence) usually appears early in the disease course. The mean age of onset is usually in the fourth decade. Affected individuals eventually become bedridden with spasticity and rigidity. The disease course ranges from two to 30 or more years (mean: 8 years).


The diagnosis is suspected in individuals with characteristic clinical and brain MRI findings and is confirmed by identification of a heterozygous pathogenic variant in CSF1R, the only gene in which pathogenic variants are known to cause ALSP.


Treatment of manifestations: Supportive management includes: attention to general care and nutritional requirements; antiepileptic drugs for seizures; and antibiotic treatment for general and recurrent infections. Prevention of secondary complications: Information about and support systems for the social problems and suicidal tendencies often associated with disease progression. Surveillance: Periodic brain MRI and clinical evaluation to monitor disease progression Agents/circumstances to avoid: Use of first-generation neuroleptics due to increased seizure risk and risk of additional parkinsonian signs; medications used to treat multiple sclerosis as they are of no benefit and have major side effects.


ALSP is inherited in an autosomal dominant manner. Individuals with ALSP usually have an affected parent; de novo mutation can occur. Each child of an individual with ALSP has a 50% chance of inheriting the pathogenic variant. Prenatal testing is possible if the pathogenic variant in a family is known.

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