ALSP Resources & FAQ

Below you can find multiple links to studies and potential treatments for ALSP.







 

Caregivers

Caregivers play an important role in the lives of individuals with ALSP. A diagnosis of ALSP can be difficult, emotional, and overwhelming for everyone involved, especially caregivers. As a caregiver, you will have questions and concerns of your own. It is important to know that while your loved one’s life may change, and yours with it, you are not alone.

By educating yourself on ALSP symptoms, long-term effects, and potential treatments, you will have information to help your loved one and yourself deal with the daily impact of ALSP on your lives. The following websites have education on caregiving and caregiver support.





 

Frequently Asked Questions

ALSP is caused by mutations in the CSF1R gene. This gene provides instructions for making a protein called colony stimulating factor 1 receptor (CSF-1 receptor), which is found in the outer membrane of certain types of cells, including glial cells. The CSF-1 receptor triggers signaling pathways that control many important cellular processes, such as cell growth and division (proliferation) and maturation of the cell to take on specific functions (differentiation).

The only available treatment option at this time is a bone marrow transplant clinical trial.
Click here to see clinical trial research regarding bone marrow transplants in treatment of ALSP.

My doctor suspects my family has the ALSP gene mutation. Are there other diseases that may be causing my symptoms?

The main differential for ALSP is leukoencephalopathy due to autosomal recessive mutations in the mitochondrial alanyl-transfer RNA (tRNA) synthetase gene (AARS2-L). Additional causes of symptoms could be:
• multiple sclerosis
• cerebral vasculitis
• CADASIL
• Alzheimer disease
• frontotemporal dementia
• atypical parkinsonism
• cortical basal degeneration
Your doctor will run all of the necessary tests to determine the cause of your symptoms. Genetic testing is available to confirm an ALSP diagnosis.

ALSP is considered a rare disease, typically manifesting between ages 30 and 50 years. Its exact prevalence is unknown, as it has been previously mistaken for many other diseases and it might thus continue to be underdiagnosed.

While ALSP is usually an inherited disease, there are case reports of proven de novo mutations and mutation carriers without clinical symptoms currently up to the age of over 70 years.

Typically, ALSP is caused by autosomal dominantly inherited mutations in the colony-stimulating factor 1 receptor (CSF1R) gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

My loved one was recently diagnosed with ALSP. What symptoms can I expect over the course of this disease?

Patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) can have a wide variety of symptoms that usually exhibit a rapid progression and lead to death within a couple of years due to progressive motor impairment. Typical symptoms are:
• apathy
• depression
• neuropsychiatric symptoms, progressing to dementia
• apraxia and rarely ataxia
• epilepsy
• motor skills are affected which causes difficulty walking.
• movement abnormalities known as parkinsonism, which includes:
• unusually slow movement (bradykinesia)
• involuntary trembling (tremor)
• muscle stiffness (rigidity)

The pattern of cognitive and motor problems is variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.
The mutations can be confirmed by genetic testing. Invitae offers a free program for anyone who may be affected by a leukodystrophy. Please visit https://www.invitae.com/en/leukodystrophies/ for more information.

ALSP was previously thought to be two separate conditions, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD), both of which cause similar white matter damage and cognitive and movement problems.

POLD was thought to be distinguished by the presence of pigmented glial cells and an absence of spheroids; however, people with HDLS can have pigmented cells, too, and people with POLD can have spheroids.

HDLS and POLD are now considered to be part of the same disease spectrum, which researchers have recommended calling ALSP.

There are doctors who specialize in adult leukodystrophies including ALSP. Refer to the section on Physician Referrals to find a doctor close to you. (To be added)
Yes. Sisters Hope Foundation provides support groups for patients, caregivers and families living with ALSP. (Refer to support group section)
We are always looking for volunteers and committee members. Monetary donations are appreciated, too.
The HDLS/ALSP Awareness ribbon represents Heather and Holly and their selfless fight to support research efforts and raise awareness to save their own children. Heather’s Hope purple and Holly’s Hope pink with zebra stripes to represent rare diseases. The sideways heart which is part of the Sisters’ Hope Foundation logo is a 3 to represent Three Sisters (Heather, Holly and Heidi).

Glossary of Terms

Printable Glossary (PDF)

ALSP: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; ALSP was formerly known as two different disorders, pigmentary orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with spheroids (HDLS)

Autosomal dominant: a pattern of inheritance where a person has one normal and one mutated copy of a gene

Axonal spheroids: swelling within part of a neuron that transmits signals; usually found with a loss of myelin

Chromosome: a long piece of DNA that carries genetic material called genes

CSF1R: colony-stimulating factor 1 receptor

CT: computed tomography combines multiple x-rays to produce a more complete image of the body

Gene: part of a chromosome that carries enough DNA to make a specific characteristic of a person

Glia: supportive cells in the nervous system

HSCT: hematopoietic stem cell therapy; a type of bone marrow transplant that uses donor stem cells to replace damaged or mutated stem cells

Leukodystrophy: rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and nerves that are caused by genetic mutations that lead to loss of myelin

Leukoencephalopathy: a type of leukodystrophy that mainly affects the brain and spinal cord

MRI: magnetic resonance imaging uses magnetic fields and radio waves to produce images of the body

Macrophage: a large white blood cell of the immune system that attacks foreign things in the body

Microglia: a type of glia cell that acts like a macrophage in the brain

Multiple sclerosis: a nervous system disease that affects the brain and spinal cord, and that damages myelin

Mutation: a change in the structure of a gene that may change the way the gene functions or what it makes

Myelin: insulating sheath around nerve fibers that help speed up neuron signals

Neurons: cells in the brain, spinal cord, and nerves that are responsible for transmitting signals from one part of the body to another

Parkinsonian tremor: an involuntary tremor that happens at rest but lessens during sleep or activity