ANO10 mutations cause ataxia and coenzyme Q10 deficiency (P2.109)

OBJECTIVE: To report 2 patients with adult-onset cerebellar ataxia, coenzyme Q10 deficiency in muscle, and ANO10 mutations. BACKGROUND: Unrevealing genetic cause of cerebellar ataxia is a challenge for clinicians and researchers. Ataxia is the most common clinical phenotype associated with CoQ10 deficiency; in particular, mutations in ADCK3 and APTX have been associated with reduced CoQ10 levels in muscle and/or fibroblasts, and cerebellar degeneration. CASE REPORT: Pt.1 is a 57 year-old woman, who developed gait disturbance, ataxia and slurred speech at age 45, and became wheelchair-bound at age 50. Pt.2 is a 52-year old woman who, at age of 30 years, presented with walking difficulties, slurred speech, and oscilloscopia. At age 50, she started to use a walker to ambulate. She also presented retinal fibrosis, cataracts, and macular degeneration. RESULTS: Neurological examination showed dysarthria, bilateral dysmetria and ataxia in both patients, while ptosis, nystagmus and mild spasticity were present only in the second one. Brain MRI revealed marked and diffuse cerebellar atrophy. Muscle histology was normal; an isolated complex III deficiency was present in the first case. Muscle CoQ10 was mildly reduced in both cases. Genetic studies revealed two heterozygous variants in ANO10 in both patients: c.132_133insT and c.1843G>A in Pt1; c.132_133insT and c.1315G>T in Pt. 2. CoQ10 supplementation led to a mild improvement of gait in both patients. CONCLUSIONS: ANO10 related cerebellar ataxia is rare and has been reported in only 5 families. Muscle biopsy and measurement of CoQ10 have never been assessed before in this condition. We found that 2 out of 40 patients in our cohort carried ANO10 mutations, suggesting that this defects should be considered in patients with unexplained ataxia and low CoQ10 in muscle. Since the two patients had mild benefit from CoQ10 supplementation, diagnosis is important in order to start therapy promptly. Disclosure: Dr. Barca has nothing to disclose. Dr. Balreira has nothing to disclose. Dr. Veronika has nothing to disclose. Dr. Pyle has nothing to disclose. Dr. Bansagi has nothing to disclose. Dr. Appleton has nothing to disclose. Dr. Graham has nothing to disclose. Dr. Hargreaves has nothing to disclose. Dr. Rasic has nothing to disclose. Dr. Lochmuller has nothing to disclose. Dr. Griffin has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Naini has nothing to disclose. Dr. Chinnery has received research support from Santhera Pharmaceuticals. Dr. Hirano has received personal compensation in an editorial capacity for Medlink. Dr. Hirano has received research support from Santhera Pharmaceutical, Pfizer Inc., and Edison Pharmaceuticals. Dr. Quinzii Hirano has nothing to disclose. Dr. Horvath has nothing to disclose.