Abstract
IntroductionSCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified. ObjectiveThe present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38. MethodsWe extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian families. All had the ELOVL5 c.689G > T (p.Gly230Val) missense mutation. ResultsAge at disease onset was in the fourth decade of life. The presenting features were nystagmus (100% of cases) and slowly progressive gait ataxia (95%). Frequent signs and symptoms included pes cavus (82%) and hyposmia (76%); rarer symptoms were hearing loss (33%) and anxiety disorder (33%). The disease progressed with cerebellar symptoms such as limb ataxia, dysarthria, dysphagia, and ophtalmoparesis followed in the later stages by ophtalmoplegia. Peripheral nervous system involvement was present in the last phase of disease with sensory loss. Dementia or extrapyramidal signs were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented cerebellar atrophy with sparing of cerebral cortex and no white matter disease. ConclusionsSCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions.
Highlights
SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified
Autosomal dominant spinocerebellar ataxias (SCAs) are a highly heterogeneous group of movement disorders characterized by gait ataxia, eye movement deficits, dysarthria, and limb ataxia, usually associated with cerebellar atrophy [1]
We recently identified SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene [8], which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells [9]
Summary
SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified. Conclusions: SCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions. Phenotypic differences seem to allow a distinction between autosomal dominant cerebellar ataxias caused by polyglutamine expansions and conventional mutations. Genetic anticipation is present in polyglutamine expansion SCAs, which generally have a disease onset in the third or fourth decade of life, inversely correlated to the number of CAG repeats in the corresponding gene [2,6]. Polyglutamine SCAs are multisystem diseases with rapid progression, while conventional mutations are generally associated with a pure form of ataxia and slow disease progression [1]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
