Autosomal dominant cerebellar ataxia type III (ORPHA:94148)
A group of neurodegenerative disorders characterized by mostly pure cerebellar syndromes with occasional non-cerebellar signs (e.g. pyramidal signs, peripheral neuropathy, writer's cramp) and includes spinocerebellar ataxia (SCA) type 5 (SCA5), SCA6, SCA11, SCA26, SCA30, and SCA31.
Epidemiology
The prevalence is unknown but varies within populations and between geographical locations. SCA6 is the most common form of this group with an estimated prevalence of less than 1/100,000. SCA31 is the second most common form and is found mainly in Japan while the other forms of ACDA type III are rarer.
Clinical description
Age of onset for these disorders is variable but is usually in adulthood. This group of disorders is characterized by mainly pure cerebellar signs such as dysarthria and gait and limb ataxia (starting with difficulty walking and loss of balance/coordination and progressing to loss of mobility and dysphagia). A spectrum of oculomotor dysfunction is also present in most patients and can include nystagmus as well as impaired vestibulo-ocular reflex and smooth pursuit. Non-cerebellar signs are less common but can include pyramidal signs (SCA11), peripheral neuropathy (SCA6), and writer's cramp (SCA5). The vast majority of these diseases have a slowly progressive course.
Etiology
Causal mutations of ACDA type III have been reported in several genes: CACNA1A (19p13) in SCA6, SPTBN2 (11q13.2) in SCA5, TTBK2 (15q15.2) in SCA11, EEF2 (19p13.3) in SCA26 and BEAN1 (16q21) in SCA31. The causal gene of SCA30 has not yet been discovered.
Diagnostic methods
Diagnosis is based on characteristic clinical findings, molecular genetic testing and magnetic resonance imaging (MRI) findings. Cerebellar atrophy with Purkinje cell degeneration is the common finding seen in all types of ACDA type III.
Differential diagnosis
Differential diagnosis includes other forms of rare hereditary ataxias, in particular other types of autosomal dominant cerebellar ataxia (see this term).
Antenatal diagnosis
Prenatal diagnosis is possible in families with a known disease causing mutation.
Genetic counseling
This group of diseases is inherited in an autosomal dominant manner and genetic counseling is possible.
Management and treatment
There is no cure for ADCA type III and treatment is supportive. Physical and occupational therapy is essential for maintaining activity along with the use of walking aids, canes and wheelchairs when necessary. Computer devices can help patients with dysarthria. Dysphagia should be monitored to decrease the risk of aspiration pneumonia. In those with vertigo, vestibular suppressants may be beneficial. Consultation with an ophthalmologist is recommended and prism glasses can help with nystagmus. Annual neurological examinations are recommended to monitor disease progression.
Prognosis
The majority of patients with ACDA type III eventually become disabled and cannot walk unassisted. Life-expectancy is slightly reduced (average age of death being 65 years or older).

                            Last update: 
                            November 2014


                            - Expert reviewer(s): 
                            Dr Shinsuke FUJIOKA  - Dr Zbigniew WSZOLEK