Differential diagnoses of replication factor complex subunit 1 cerebellar ataxia, neuropathy and vestibular areflexia syndrome and its disease spectrum
| Cause | Key features | |
| Sensory neuropathy/neuronopathy | ||
| Acquired causes | Paraneoplastic | History of neoplasms, subacute onset, antineuronal antibodies, cerebrospinal fluidanalysis |
| Immune-mediated | Autoantibody screen, systemic involvement | |
| Toxic/metabolic (diabetes mellitus type 2, B12 deficiency, copper deficiency) | Blood test | |
| Toxic | Platin-derived treatment, B6 intoxication | |
| Hereditary causes | Hereditary sensory neuropathy RNF17022 23 | Early onset, insensitivity to pain, painless ulcerations Dominant family history, normal cerebellar function |
| Late-onset cerebellar ataxia | ||
| Acquired causes | Multiple system atrophy24 25 | Early and severe dysautonomia, parkinsonism, rapid eye movement sleep behaviour disorders, MR scan of brain findings (hot-cross bun sign) |
| Paraneoplastic | Subacute onset, antineuronal antibodies, CSF analysis | |
| Toxic/metabolic | Thiamine deficiency/alcoholic abuse | |
| Vascular | Acute onset, cerebrovascular risk factors | |
| Inflammatory | Subacute onset, MR scan of brain findings, CSF analysis | |
| Idiopathic late onset cerebellar ataxia | Progressive late-onset ataxia without known cause | |
| Hereditary causes | Friedreich’s ataxia26–28 | Onset <25 years, pyramidal signs, scoliosis, pes cavus, systemic involvement (cardiac, endocrine, ocular) |
| SCA3 (late-onset Machado-Joseph disease)29 | Autosomal dominant, extrapyramidal features, S-M neuropathy, progressive external ophthalmoplegia | |
| Gerstmann-Straussler-Scheinker syndrome30 31 | Cognitive impairment, more rapid progression | |
| Bilateral vestibular areflexia | ||
| Acquired causes | Ototoxic drugs, Menière’s syndrome, vestibular neuritis, tumours, infections, inflammation | More commonly unilateral, cochlear symptoms |
| Hereditary causes | SCA (SCA types 1, 2, 3, 6)32 | Autosomal dominant, mild vestibular impairment, additional signs |
| Charcot-Marie-Tooth disease33–35 | Sensorimotor neuropathy | |
| Usher syndrome type I and II36 37 | Deafness, retinitis pigmentosa | |
| Complex neurological diseases | ||
| Mitochondrial diseases | Polymerase gamma38 | Ophthalmoplegia, multisystem involvement |
MR, magnetic resonance; SCA, spinocerebellar ataxia.