José Gazulla1, Elvira Orduna-Hospital2, Isabel Benavente3, Ana Rodríguez-Valle4, Pedro Osorio-Caicedo5, Sara Alvarez-de Andrés6, Elena García-González7, Jesús Fraile-Rodrigo8, Francisco Javier Fernández-Tirado2, José Berciano9. 1. Department of Neurology, Hospital Universitario Miguel Servet, Isabel la Católica 1-3, 50009, Zaragoza, Spain. josegazulla@gmail.com. 2. Department of Ophthalmology, Hospital Universitario Miguel Servet, Zaragoza, Spain. 3. Department of Clinical Neurophysiology, Hospital San Jorge, Huesca, Spain. 4. Section of Genetics, Department of Clinical Biochemistry, Hospital Universitario Miguel Servet, Zaragoza, Spain. 5. Department of Clinical Neurophysiology, Hospital Universitario Miguel Servet, Zaragoza, Spain. 6. NIMGenetics, Madrid, Spain. 7. Department of Clinical Biochemistry, Hospital Universitario Miguel Servet, Zaragoza, Spain. 8. Department of Otolaryngology, Hospital Universitario Miguel Servet, Zaragoza, Spain. 9. Department of Neurology, CIBERNED, Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander, Spain.
Abstract
OBJECTIVE: To report clinical and ancillary findings in a kindred with spinocerebellar ataxia 38 (SCA38). PATIENTS AND METHODS: Five family members spanning two generations developed gait ataxia and intermittent diplopia. On examination, a cerebellar syndrome accompanied by downbeat nystagmus and a saccadic head impulse test (HIT) were found. RESULTS: Whole-exome sequencing demonstrated a heterozygous variant in ELOVL5, c.779A > G (p.Tyr260Cys), in four tested patients. Intermittent concomitant esotropia and hypertropia caused transient diplopia in one individual each. Saccadic HIT responses were found in four subjects. Sensorineural hypoacusis was present in every case. Electrophysiological studies demonstrated a sensory neuronopathy in patients from the first generation, with prolonged disease duration. Baseline serum docosahexaenoic acid (DHA) percent was diminished in four individuals. Oral 26-week dietary DHA supplementation, 650 mg/day, raised serum DHA percent and induced a statistically significant reduction in Scale for the Assessment and Rating of Ataxia (SARA) total scores, and in stance and heel-shin slide item scores. CONCLUSION: The mentioned ELOVL5 variant segregated with disease in this kindred. Downbeat nystagmus, intermittent heterotropia causing transient diplopia, vestibular impairment demonstrated by abnormal HIT, and sensory neuronopathy were part of the clinical picture in this series. DHA supplementation raised serum DHA percent in cases with diminished levels, and induced a clinical amelioration and a statistically significant reduction in SARA scores in the study group. Further studies are needed to investigate the role of these findings in SCA38, and to determine the response to prolonged DHA supplementation.
OBJECTIVE: To report clinical and ancillary findings in a kindred with spinocerebellar ataxia 38 (SCA38). PATIENTS AND METHODS: Five family members spanning two generations developed gait ataxia and intermittent diplopia. On examination, a cerebellar syndrome accompanied by downbeat nystagmus and a saccadic head impulse test (HIT) were found. RESULTS: Whole-exome sequencing demonstrated a heterozygous variant in ELOVL5, c.779A > G (p.Tyr260Cys), in four tested patients. Intermittent concomitant esotropia and hypertropia caused transient diplopia in one individual each. Saccadic HIT responses were found in four subjects. Sensorineural hypoacusis was present in every case. Electrophysiological studies demonstrated a sensory neuronopathy in patients from the first generation, with prolonged disease duration. Baseline serum docosahexaenoic acid (DHA) percent was diminished in four individuals. Oral 26-week dietary DHA supplementation, 650 mg/day, raised serum DHA percent and induced a statistically significant reduction in Scale for the Assessment and Rating of Ataxia (SARA) total scores, and in stance and heel-shin slide item scores. CONCLUSION: The mentioned ELOVL5 variant segregated with disease in this kindred. Downbeat nystagmus, intermittent heterotropia causing transient diplopia, vestibular impairment demonstrated by abnormal HIT, and sensory neuronopathy were part of the clinical picture in this series. DHA supplementation raised serum DHA percent in cases with diminished levels, and induced a clinical amelioration and a statistically significant reduction in SARA scores in the study group. Further studies are needed to investigate the role of these findings in SCA38, and to determine the response to prolonged DHA supplementation.
Authors: Deborah A Sival; Martinica Garofalo; Rick Brandsma; Tom A Bokkers; Marloes van den Berg; Tom J de Koning; Marina A J Tijssen; Dineke S Verbeek Journal: Diagnostics (Basel) Date: 2020-11-24