About
What Causes ALSP?
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). 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.
ALSP may also be referenced as CSF1R-related leukoencephalopathy.
hdls and pold not diagnosed as alsp
ALSP Prevalence
ALSP is one of a group of adult-onset leukodystrophy disorders. It is estimated that approximately 10,000 people are affected by ALSP in the United States, with similar prevalence in Europe and Japan.
ALSP is caused by an autosomal-dominant genetic mutation.  If one parent has it, there is a 50% chance a child will have it
ALSP makes up 10 to 25% of adult-onset leukodystrphoies.
Average age of dianosis is 43 years old
Neuron with spheroid
ALSP can cause lesions in the brain due to a loss of myelin, a protective layer for brain cells (neurons). Neurons in patients with ALSP can develop a change in shape, called a spheroid, which can stop the neuron from sending signals to other parts of the brain or body.1-2

Available Treatment
There are currently no FDA-approved treatments for ALSP. Those who have it experience a wide range of symptoms. Several existing medications are being used off-label to treat ALSP symptoms. The term “off-label” means the medication is being used in a manner not specified in the FDA's approved packaging label or insert. Some of these medications include anti-depressants, muscle relaxers, anti-epileptic medications for patients with seizures, and antibiotics for patients that develop pneumonia and urinary tract infections.4

Physical therapy may be used to help with movement and muscle problems that result from ALSP. For any genetic disease, psychological and genetic counseling are commonly recommended to cope with mental and physical symptoms as well as the potential risk of inheritance of ALSP in other family members.

What to Expect
Everyone’s journey with ALSP is different. ALSP can present with different symptoms within the same family. The course of ALSP can range from 2 to over 30 years.2

ALSP is a progressive disease that is characterized by issues with judgement, personality and psychological changes, and problems with movement.

It is important for people with ALSP to build a support system including family, friends, caregivers, advocacy organizations, and medical professionals to help navigate their symptoms and improve their quality of life.

References
  1. Sassi C, Nalls MA, Ridge PG, et al. Mendelian adult-onset leukodystrophy genes in Alzheimer's disease: Critical influence of CSF1R and NOTCH3. Neurobiol Aging. 2018;179:e17-179.e29.
  2. Sundal C, Wszolek ZK. CSF1R-Related Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia. 2012 Aug 30 [Updated 2017 Oct 5]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK100239/
  3. 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.
  4. Konno T, Kasanuki K, Ikeuchi T, et al. CSF1R-related leukoencephalopathy: A primary player in primary microgliopathies. Neurology. 2018;91(24):1092-1104.
Genetics
chromosome-5

ALSP is a disease caused by a rare mutation in the CSF1R gene on chromosome 5.1-2 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.3 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.

The CSF1R mutation affects cells within the body that are part of the immune system. These cells are called macrophages and microglia.2,4 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.

For information about a no-charge genetic testing program, please visit the Detect Leukodystrophy page here

Genetics of Autosomal Dominant Disorders
  1. Konno T, Kasanuki K, Ikeuchi T, et al. CSF1R-related leukoencephalopathy: A primary player in primary microgliopathies. Neurology. 2018;91(24):1092-1104.
  2. Sundal C, Wszolek ZK. CSF1R-Related Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia. 2012 Aug 30 [Updated 2017 Oct 5]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK100239/
  3. Asadi S, Jamali M, Amjadi H. Assessment of genetic mutation CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia syndrome. CP Allergy Immunol. 2018;1(1):003.
  4. 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.
HOPE & LOVE
are stronger than fear