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ADCK 3 mutations with epilepsy, stroke‐like episodes and ataxia: a POLG mimic?
Author(s) -
Hikmat O.,
Tzoulis C.,
Knappskog P. M.,
Johansson S.,
Boman H.,
Sztromwasser P.,
Lien E.,
Brodtkorb E.,
Ghezzi D.,
Bindoff L. A.
Publication year - 2016
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13003
Subject(s) - medicine , ataxia , epilepsia partialis continua , epilepsy , encephalopathy , pathology , cerebellar ataxia , stroke (engine) , status epilepticus , psychiatry , mechanical engineering , engineering
Background and purpose Defects of coenzyme Q10 (CoQ10) metabolism cause a variety of disorders ranging from isolated myopathy to multisystem involvement. ADCK 3 is one of several genes associated with CoQ10 deficiency that presents with progressive cerebellar ataxia, epilepsy, migraine and psychiatric disorders. Diagnosis is challenging due to the wide clinical spectrum and overlap with other mitochondrial disorders. Methods A detailed description of three new patients and one previously reported patient from three Norwegian families with novel and known ADCK 3 mutations is provided focusing on the epileptic semiology and response to treatment. Mutations were identified by whole exome sequencing and in two measurement of skeletal muscle CoQ10 was performed. Results All four patients presented with childhood‐onset epilepsy and progressive cerebellar ataxia. Three patients had epilepsia partialis continua and stroke‐like episodes affecting the posterior brain. Electroencephalography showed focal epileptic activity in the occipital and temporal lobes. Genetic investigation revealed ADCK 3 mutations in all patients including a novel change in exon 15: c.T1732G, p.F578V. There was no apparent genotype−phenotype correlation. Conclusion ADCK 3 mutations can cause a combination of progressive ataxia and acute epileptic encephalopathy with stroke‐like episodes. The clinical, radiological and electrophysiological features of this disorder mimic the phenotype of polymerase gamma ( POLG ) related encephalopathy and it is therefore suggested that ADCK 3 mutations be considered in the differential diagnosis of mitochondrial encephalopathy with POLG ‐like features.