Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family

SCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on the STUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) was performed. Brain magnetic resonance imaging (MRI), including DTI, and single-photon emission computed tomography (SPECT) were used to study the primarily affected tracts and regions. WES revealed the previously reported heterozygous truncating mutation in ubiquitin ligase domain of STUB1 (ENST00000219548:c.823_824delCT, ENSP00000219548:p.L275Dfs*16) leading to a frameshift. Patient’s cognitive status was compatible with CCAS. Novel clinical features different from the original report include later onset chorea, dystonia, general slowness of movements, apraxia, and palilalia, some of which have been recently reported in two families with different STUB1 mutations. CCAS is a prominent and often early feature of SCA48 which may be followed years after the onset of the disease by other complex neurological signs and symptoms. DTI may be helpful for demonstrating the cerebello-frontal tracts, involved in CCAS-associated SCA48, the differential diagnosis of which may be challenging especially in its early years.