Table 2.
Genetic, clinical, laboratory and conventional MRI in most common recessive ataxias [modified from Anheim et al. (ref. 125)]
| Disease | Gene and protein | Age at onset | Key symptoms in addition to cerebellar ataxia | Laboratory findings | Conventional MRI |
|---|---|---|---|---|---|
| Cerebellar ataxias with pure sensory neuropathy | |||||
| FRDA | FXN frataxin | 2–60 mean 16 | Bilateral Babinski sign, scoliosis, square-wave jerks | GAA triplet repeat expansion in intron1 of FXN gene | Spinal cord and bulbar atrophy, symmetric T2 high signal in posterior and lateral columns of the spinal cord |
| AVED | TTPA alpha-tocopherol transfer protein | 2–50 mean 17 | Bilateral Babinski sign, scoliosis, retinitis pigmentosa | Decreased serum level of vitamin E | Spinal cord atrophy |
| Cerebellar ataxia with sensorimotor axonal neuropathy | |||||
| AT | ATM Ataxia Telangectasia mutated | 2–3 | Conjuctival telangectasias, dystonia, chorea, susceptibility to infections and cancer | Elevated serum Alpha-feto-protein, immunoglobulin deficiency, specific karyotype | Cerebellar atrophy brain T2 hypointense dots |
| AOA 1 | APT aprataxin | 1–20 mean 7 | Oculocephalic dissociation, chorea, dystonia | Elevated serum LDL cholesterol, low serum albumin | Cerebellar Atrophy |
| AOA2 | SETX senataxin | 7–25 mean 15 | Oculocephalic dissociation, chorea, dystonia | Elevated serum Alpha-feto protein | Cerebellar Atrophy |
| ARSACS | SACS sacsin | Up to 12 mean 2 | Spastic paraparesis, distal amyotrophy to 4 arms, pes cavus, scoliosis | Atrophy of superior vermis, thinned corpus callosum, T2 hypointense stripes in a bulky pons, T2 hyperintense rim around the thalami | |
| CTX | CYP27 Sterol27 hydoxylase | Childhood | Sensory neuropathy, spasticity | Elevated serum cholestanol | Cerebellar atrophy, cerebellar and cerebral WM T2 hyperintensity |
| Cerebellar ataxia without neuropathy | |||||
| JSRD | 10 causative genes encoding for proteins of the primary cilium (see ref [126]) | Neonatal period | Hypotonia, oculomotor apraxia, facial dysmorphism, irregular neonatal breathing, cognitive impairment, involvement of kidneys, liver, eyes | “Molar tooth”, vermal hypoplasia, enlarged IV ventricle and posterior fossa | |
| ARCA1 | SYNE1 Spectrin | 17–46 mean 32 | Pure ataxia | Cerebellar atrophy | |
| ARCA2 | ADCK3 Aarf-domain containing Kinase 3 | 1–11 mean 4 | Mental retardation, myoclonus, epilepsy, stroke like episodes | Elevated serum lactic acid, decreased coenzyme Q10 | Cerebellar atrophy, stroke-like lesions |
| NPC | NPC1 | 2–30 | Vertical supranuclear ophthalmoplegia, dystonia, cognitive impairment | Skin biopsy findings | Variable cerebral and cerebellar atrophy |
| NPC1 | |||||
| NPC2 | |||||
| NPC2 | |||||
AOA1 ataxia with oculomotor apraxia type 1; AOA2 ataxia with oculomotor apraxia type 2; ARCA1 autosomal recessiva cerebellar ataxia type 1; ARCA2 autosomal recessive cerebellar ataxia type 2; ARSACS autosomal recessive spastic ataxia of Charlevoix-Saguenay; AT ataxia telangectasia; AVED ataxia with vitamin E deficiency; CTX cerebrotendineous xanthomatosis; FRDA Friedreich's ataxia; JSRD Joubert syndrome and related disorders (ciliopathies); NPC Niemann–Pick type C