Table 2 Natural history of mt-aaRS-related leukodystrophies

Mean age at onset (age range)

8 years (5 months–40 years)

6 months (birth–16 months)

25 years (1.5–44 years)

Rate of disease progression

Slow, gradual >

rapid decline

Biphasic with stability or improvement after early “hit”

Rapid decline within a few years

Risk of disability

Greater disability associated with earlier age of onset

Greater disability associated with initial clinical and imaging severity

High risk of motor and cognitive impairment

Risk of mortality

Increased for infantile-onset disease, otherwise low

Increased for early onset, severe disease with multi-organ involvement

Increased risk from late disease complications