Ataxia with oculomotor apraxia (AOA1, AOA2)
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A teenager with a 5-year history of progressive cerebellar ataxia is unable to initiate horizontal saccades; head thrusts compensate ("oculomotor apraxia"). MRI shows cerebellar atrophy. Labs reveal hypoalbuminemia and elevated cholesterol with low albumin. Alpha-fetoprotein is normal (AOA1) or markedly elevated (AOA2).
Two related autosomal recessive ataxias caused by defects in DNA single-strand break repair:
| Subtype | Gene | Onset | Distinguishing labs |
|---|---|---|---|
| AOA1 | APTX (aprataxin) | Childhood (~5 yrs) | Hypoalbuminemia, hypercholesterolemia; AFP normal |
| AOA2 | SETX (senataxin) | Adolescence (~15 yrs) | AFP elevated; albumin normal |
Both AR. APTX and SETX participate in resolving DNA single-strand break intermediates; their loss causes neuronal genome instability.
- Progressive cerebellar ataxia: gait, then limb, then dysarthria
- Oculomotor apraxia: inability to initiate voluntary horizontal saccades; patients use head thrusts to redirect gaze. Subtle and easily missed.
- Peripheral neuropathy: distal weakness, areflexia (axonal sensorimotor)
- Choreoathetosis in AOA1
- Cognitive function preserved: distinguishes from ataxia-telangiectasia
- No telangiectasias, no immunodeficiency, no cancer predisposition: distinguishes from A-T
- Clinical (ataxia + oculomotor apraxia + neuropathy in a young patient)
- Lab discriminators:
- AOA1: low albumin (often <3 g/dL), high cholesterol, normal AFP
- AOA2: high AFP (often 3-15× normal), normal albumin
- Brain MRI: cerebellar atrophy
- Confirmatory: APTX / SETX sequencing
- Ataxia-telangiectasia (A-T): overlapping (ataxia + oculomotor apraxia + elevated AFP), but A-T adds telangiectasias, immunodeficiency, lymphoma risk, radiosensitivity, ATM, none of which appear in AOA. The single most useful clinical discriminator is AFP: elevated in BOTH A-T and AOA2 but normal in AOA1.
- Friedreich ataxia: FXN GAA repeat, cardiomyopathy, scoliosis, no oculomotor apraxia
- Spinocerebellar ataxias (SCAs): autosomal dominant, repeat expansions
- Ataxia with vitamin E deficiency (AVED): TTPA, treatable; check vitamin E levels
- No disease-modifying therapy. Supportive care.
- PT/OT for ataxia and neuropathy
- Speech therapy for dysarthria; AAC devices in advanced disease
- Surveillance MRI as clinically indicated
- Genetic counseling: AR, 25% recurrence; siblings testable
"AOA1 = Albumin Low (Aprataxin), AOA2 = AFP High (Senataxin)": pair the lab abnormality with the gene name to keep the two subtypes straight.
Ataxia + oculomotor apraxia → check AFP and immune status. If AFP is elevated AND telangiectasias/IgA low, you're looking at A-T, not AOA. AOA has the same eye sign without the immune/cancer risk.