Understanding ALSP
What causes ALSP?
ALSP is an acronym for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. It is a rare genetic disease caused by a defect in the DNA, or mutation, of the CSF1R gene. When there is a mutation in the CSF1R gene, certain brain cells, called microglia, malfunction and lose their ability to protect the brain, leading to ALSP symptoms.
Lisa, living with ALSP
Healthy microglia
ALSP is caused by loss-of-function mutations in the CSF1R gene, which lead to microglial dysfunction
ALSP makes up about 10% of adult-onset leukodystrophies and is estimated to affect approximately 10,000 people in the United States, 15,000 in Europe and the United Kingdom, and 4,000 in Japan. However, since the disease is rare, it is difficult to predict exactly how many people live with ALSP.
A diagnosis of ALSP can be challenging and overwhelming, and it can raise many questions. Learning about ALSP and knowing what to expect can help individuals, caregivers and families understand the disease and prepare for the future.
Symptoms and Impact of ALSP
ALSP affects every person differently. The symptoms and progression of ALSP can vary even among family members. ALSP is a progressive disease, meaning that a diverse range of symptoms will develop at different times and become more severe as time passes. On average symptoms first appear around age 43, but may appear in the age range of 18-78 years old.1,2 Symptoms often begin with mild memory, thinking, and behavioral changes and progress to developing movement disorder symptoms and cognitive impairment.
Diagnosis
ALSP is a disease caused by a rare mutation in the CSF1R gene on chromosome 5. It is an autosomal dominant disease, meaning 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 childbearing years, many individuals have already had children by the time they are aware they have the disease.
Symptoms of ALSP can overlap with other neurological conditions, such as, frontotemporal dementia (FTD), multiple sclerosis (MS), alzheimer’s disease (AD) and other adult-onset leukodystrophies. Genetic testing for the CSF1R mutation can confirm an ALSP diagnosis. In addition to genetic testing, an MRI (Magnetic resonance image) can verify lesions, or damaged areas in the brain, caused by the loss of myelin, a protective layer for brain cells, around neurons (nerve cell). CT scans can detect other abnormal areas in the brain.
Click here to learn more about diagnosis for ALSP.
White spots on an MRI could mean damage to neurons and myelin, and larger spots (arrows) could be indicative of ALSP. 1,3
Visit www.informeddna.com/ALSPAware to find out how to access genetic testing services.
Symptom Management
There are currently no FDA (U.S. Food and Drug Administration)-approved therapies for ALSP. Existing care and management practices focus on symptom relief and maintaining quality of life. Commonly prescribed treatments do not target the cause or slow the progression of ALSP. A care plan for ALSP may include:
Medications that temporarily alleviate motor, mood, and behavior symptoms like antidepressants, muscle relaxants, and antiseizure medications.
Supportive therapies including physical, occupational, and speech therapies, which may help individuals maintain abilities and quality of life.
References:
Konno T, Yoshida K, Mizuno T, et al. Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation. Eur J Neurol. 2017;24(1):37-45.
Sundal C, Wszolek Z. CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. 2012 Aug 30 [Updated 2017 Oct 5]. In: Adam MP MG, Pagon RA, et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2023.
With ALSP, bilateral white matter lesions may also appear in the frontal and parietal regions of the brain.
