Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurological disease caused by an autosomal dominant genetic mutation in the CSF1R gene (colony-stimulating factor 1 receptor) on chromosome 5. An autosomal dominant disease means that each child born to someone who has the CSF1R gene mutation has a 50% chance of also having this mutation. Because ALSP is often diagnosed after the childbearing years, most individuals have already had children by the time they are aware they have the disease. Currently there is no newborn genetic testing for the CSF1R gene mutation that causes ALSP since this is considered an adult-onset disease.
ALSP was previously known as two diseases: hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). After the discovery of the gene mutation, these two diseases have become known as one entity: ALSP.
The CSF1R mutation affects cells within the body that are part of the immune system. These cells are called macrophages and microglia. The mutation causes neurons to be misshapen due to the presence of spheroids in part of the cell. Macrophages take myelin away from the misshaped neurons which causes further damage. The CSF1R mutation also leads to underactive microglia, cells that are normally protective for neurons. The combination of neuron spheroids, lack of myelin, and underactive microglia are what cause the symptoms of ALSP.
ALSP is one of a group of adult-onset leukodystrophy disorders. Because it is a rare disease, the actual number of cases are unknown.
Sisters’ Hope Foundation would like to thank https://www.alspinfo.com/ for allowing us to share some of their informative materials about ALSP and the CSF1R mutation.