AARS2-related leukodystrophy
Ovarioleukodystrophy (females)
Inheritance:
Autosomal recessive
Inheritance from both parents will result in the disease
Age range at onset:
Children and adults
Specialists you may see:
Geneticist
Symptoms
AARS2-related leukodystrophy causes dementia, upper motor neuron signs and ataxia. Ovarian failure is common in females with these mutations.
Personality changes are a common and early symptom of AARS2-related leukodystrophy, including depression, anxiety and loss of social inhibitions. Memory loss and the loss of ability to plan and implement actions will follow. Mild seizures may occur early in the disease progression.
Walking difficulties become apparent as the condition progresses, with movement issues developing to include bradykinesia, tremors and rigidity. Eventually the affected individual becomes unable to walk, talk or care for themselves.
Cause
Mutations in the AARS2 (alanyl-transfer [t]RNA synthetase 2) gene cause AARS2-related leukodystrophy. This gene codes for a protein involved in the health of mitochondria.
In adults, there are many similarities to the symptoms and signs of Hereditary Diffuse Leukoencephalopathy with axonal Spheroids (HDLS), although AARS2-related leukodystrophy is autosomal recessive, while HDLS is autosomal dominant. Unlike HDLS, AARS-2 related leukodystrophy can also affect children.
Ovarian failure in females can be an indicator that the condition is related to AARS2 as opposed to CSF1R (as in HDLS), but there is no such indicator in males.