Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations.
Mutations in POLG gene are responsible for a wide spectrum of clinical disorders with altered mitochondrial DNA (mtDNA) integrity, including mtDNA multiple deletions and depletion. Sensory ataxic neuropathy with ophthalmoparesis (SANDO) caused by mutations in POLG gene, fulfilling the clinical triad of sensory ataxic neuropathy, dysarthria and/or dysphagia and ophthalmoparesis, has described in a few reports. Here we described five cases of adult onset autosomal recessive sensory ataxic neuropathy with ophthalmoplegia. All patients had ataxia, neuropathy, myopathy, and progressive external ophthalmoplegia (PEO). The muscle pathology revealed ragged-red and cytochrome c oxidase (COX) negative fibers in three patients. However, deficiencies in the activities of mitochondrial respiratory chain enzyme complexes were not detected in any of the patients' muscle samples. Multiple deletions of mtDNA were detected in blood and muscle specimens but mtDNA depletion was not found. Due to these diagnostic difficulties, POLG-related syndromes are definitively diagnosed based on the presence of deleterious mutations in the POLG gene.
Milone
Margherita
M
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Brunetti-Pierri
Nicola
N
Tang
Lin-Ya
LY
Kumar
Neeraj
N
Mezei
Michelle M
MM
Josephs
Keith
K
Powell
Suzanne
S
Simpson
Ericka
E
Wong
Lee-Jun C
LJ
D000328:Adult; D001763:Blepharoptosis / Q000209:etiology / Q000235:genetics; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004401:Dysarthria / Q000150:complications / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D015417:Hereditary Sensory and Motor Neuropathy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009886:Ophthalmoplegia / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010292:Paresthesia / Q000209:etiology / Q000235:genetics; D010375:Pedigree; D013385:Succinate Dehydrogenase / Q000235:genetics; D013577:Syndrome
D004247:DNA; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human