Early onset ataxia (EOA) is a highly heterogeneous group of degenerative and metabolic diseases, mostly due to genetic causes with autosomal-recessive inheritance. Friedreich’s ataxia is the most frequent cause in Western countries but little is known about the frequency of other genotypes. Ataxia with ocular apraxia types 1 and 2 (AOA1 + AOA2) have been reported to be the next frequent subtypes in European populations. However, polymerase gamma (POLG) mutations may be even more frequent, at least in the German population. Likewise, autosomal recessive spastic ataxia Charlevoix Saguenay (ARSACS) seems to be substantially more frequent than previously estimated, as recently shown in a cohort of Dutch patients. In contrast, ataxia teleangiectasia (AT) seem to be less frequent then reported in earlier studies. For many other subtypes epidemiological data are missing and their complete phenotypic spectrum is still unknown as descriptions often rely on reports of only few families.
Recent efforts of the EUROSCA consortium defined clinical features, MRI morphology and electrophysiological characteristics of autosomal dominant ataxias. Additionally, EUROSCA set off to analyse the natural history of the more frequent SCA genotypes. This provides essential data to calculate numbers needed to treat and study duration for therapeutical trials.
Such data are still missing for autosomal recessive ataxias with early
onset. This project sets off to assess phenotypic characteristics and
the natural history of EOA and thus to provide essential data for
upcoming interventional studies. Additionally, this study aims to
prepare the ground for an application, e.g. to the EU, on a
comprehensive genetic characterization of EOA.
Principal investigator: Ludger Schöls, MD
Contact person: Matthis Synofzik, MD
Dept. of Neurodegenerative Diseases
Center of Neurology
72076 Tübingen, Germany
Prospective, multicenter observational study.
To assess phenotypic characteristics and progression of disease in patients with early onset ataxia in a prospective natural history study.
- To assess neuroimaging findings in EOA
- To reveal electrophysiological characteristics in EOA
- To analyse serum markers in EOA (e.g. AFP, cholesterol, albumin, lactate)
- To identify psychiatric and cognitive co-morbidities in EOA
- To assess quality of life in EOA
- To compile experience of the therapeutic benefit of from compassionate drug use
- To analyse effects of co-medication (side-effects as well as beneficial effects)
For EOA with previously established genetic diagnosis
- To compare regional frequency of genotypes
- To define the phenotypic spectrum of EOA subtypes
- To decipher clinical features, electrophysiological characteristics, neuroimaging findings and metabolic markers indicating the underlying genotype
- To gather a cohort of genetically undefined EOA for further genetic studies
- To establish a DNA bank of EOA with optional extension to more extensive biobanking