Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) in late life due to compound heterozygous POLG mutations.
Missense mutations in the gene for polymerase gamma 1 (POLG1) cause a number of phenotypically heterogeneous mitochondrial diseases, most commonly progressive external ophthalmoplegia, and are characterized by the accumulation of multiple, large-scale deletions of mitochondrial DNA. The triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) has been demonstrated in a small subset of patients with POLG1 mutations. We report a sporadic case of an 80-year-old compound heterozygote man who presented with SANDO and was found to have three known pathogenic mutations in the POLG1 gene (p.T251I/p.P587L/p.G848S). To our knowledge, none of these mutations have been demonstrated previously in SANDO. This patient's late presentation illustrates that a mitochondrial disorder should be considered regardless of age if the clinical symptoms warrant.
Weiss
Michael D
MD
Department of Neurology, University of Washington Medical Center, Box 356115, 1959 NE Pacific Street, Seattle, Washington 98195, USA. mdweiss@u.washington.edu
Saneto
Russell P
RP
D000369:Aged, 80 and over; D001259:Ataxia / Q000235:genetics* / Q000473:pathology; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004172:Diplopia / Q000235:genetics; D004401:Dysarthria / Q000235:genetics* / Q000473:pathology; D005141:Eyelid Diseases / Q000235:genetics; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000473:pathology; D020125:Mutation, Missense; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D014832:Voice Disorders / Q000235:genetics
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human