Introduction
- AARS2-RD is a type of leukodystrophy, a group of genetic disorders affecting the white matter of the brain.
- Previously classified under adult-onset leukoencephalopathy with axonal spheroids (ALSP).
- The term ALSP is being phased out due to multiple genetic causes leading to similar phenotypes.
- Classification is now based on the specific genetic variants involved.
- Disorders linked to these genes can manifest in childhood and present beyond the traditional ALSP spectrum.
Clinical Types of ALSP
- CSF1R-related ALSP: Most commonly associated with adult-onset white matter degeneration and axonal spheroids.
- AARS2-RD: Previously referred to as ovario-leukoencephalopathy; now recognized as a distinct genetic disorder.
- HDLS-S (Swedish type): Caused by pathogenic variants in the ARAS/AARS1 gene.
- AARS/AARS2/CSF1R-negative ALSP: Likely caused by as-yet unidentified genetic variants.
Subtypes of AARS2-Related Disorder
- Infantile-onset cardiomyopathy: Presents early in life with severe cardiac involvement.
- AARS2-related leukoencephalopathy: Typically manifests later with white matter involvement and progressive neurological symptoms.
Genetics
- AARS2-RD is inherited in an autosomal recessive pattern.
Synonyms
- AARS2-RD
- Novel (ovario) leukodystrophy related to AARS2 gene variants
- Hereditary diffuse leukoencephalopathy with spheroids (HDLS), excluding some CSF1R-RD families and Swedish HDLS
- AARS2 infantile onset cardiomyopathy
Subdivisions
- AARS2-related infantile onset cardiomyopathy: Also known as “infantile-onset cardiomyopathy” and “combined oxidative phosphorylation deficiency 8”
- AARS2-related adult-onset leukoencephalopathy: Also known as “neurodegeneration with or without leukoencephalopathy” and “leukoencephalopathy, progressive, with ovarian failure”
Signs & Symptoms
General Overview
- Symptoms vary by age of onset
- In early childhood, severe cardiomyopathy predominates
- In adulthood, neurological decline and premature ovarian failure in females
AARS2-related Infantile Onset Cardiomyopathy
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