Basal ganglia involvement of a patient with SCA 17

Sirs: We describe a patient with spinocerebellar ataxia 17 (SCA17), a condition that has recently been linked to an abnormal CAG expansion in the TATA-binding protein, a general transcription factor [4–7]. A 35-year-old male was referred to our hospital with a five year history of slowly progressive speech disorder and a one year history of dysphagia. The patient recalled “movement problems” in his father’s mother who died with dementia of unknown aetiology at age 57 years. A son of his father’s brother started to experience cognitive deficits, speech problems and loss of fine motor skills at the age of 31 years. The father, however, has never experienced any neurological problems. Neurological examination revealed marked cerebellar dysarthria, a diminished gag reflex, but no other neurological abnormalities. Mild cognitive impairment was suggested with a Mini Mental State (MMS) of 26 (maximum 30) and SISCO (SIDAM) score of 40 (maximum 55) points. Laboratory findings were normal. The cerebrospinal fluid (CSF) analysis showed a total protein concentration of 675 mg/l, other results were normal. Brain stem auditory evoked potentials (BEAP) detected a mesencephalic lesion bilaterally. The latencies of the masseter and blink reflex responses were within normal limits. Electrooculography revealed hypometric saccades. Magnetic resonance imaging demonstrated cortical cerebellar atrophy. Striatal dopamine transporter (DAT) availability and striatal dopamine D2 receptor (D2R) were measured with [123I]FP-CIT, and [123I]IBZM (Amersham Health), respectively, applying a brain dedicated single-photon emission computed tomography (SPECT) system (Ceraspect, DSI) and an MRI-based region of interest (ROI) technique to calculate specific-to-non-specific binding ratios. DAT availability was 23–25 % lower than our agematched controls at baseline [right striatum: 4.43 vs. 5.74 ± 1.40 [mean ± SD], 95 %-confidence interval: upper limit 6.80, lower limit 5.09, left striatum: 4.25 vs. 5.67 ± 1.23 (6.74, 5.07), reference region: occipital cortex], which was clearly beyond our test-retest variability [3]. This reduction declined over a twoyear follow-up period (ratios: 3.10, right striatum, 3.24, left striatum, Fig. 1). Positron emission tomography (PET) with [18F]Fluorodeoxyglucose revealed a reduced striatal glucose metabolic rate (32.7 μmol/ min/100 mL brain tissue), which exceeds an only slightly diminished D2R binding capacity [right striatum: 2.18 vs. 2.34 ± 0.20 (2.46, 2.21), left striatum: 2.13 vs. 2.32 ± 0.15 (2.43, 2.18), reference region: frontal cortex, Fig. 2]. Neither abnormalities in the cerebral cortical and cerebellar glucose metabolic rate (36.6 μmol/min/100 mL, and 35.3 μmol/min/100 mL, respectively) nor significant follow-up changes of glucose metabolism and D2R binding capacity were found. An oesophagogram and videocinematography revealed dysphagia and a prolonged pharyngeal phase. In conclusion, an autosomal dominant degenerative disorder involving cerebellum and basal ganglia was diagnosed. Genotyping revealed an abnormal expansion in the TATA-binding protein (TBP) gene demonstrating one allele with one pathological expanded fragment of TBP gene with 50 CAG repeats and one normal allele with 37 CAG repeats (normal range: 27 to 44 CAG repeats) confirming spinocerebellar ataxia SCA 17. LETTER TO THE EDITORS