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
- 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.
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.
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:
- neuropsychiatric symptoms, progressing to dementia
- apraxia and rarely ataxia
- 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)
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.