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.
Department of Neurology, University of Washington Medical Center, Box 356115, 1959 NE Pacific Street, Seattle, Washington 98195, USA. mdweiss@u.washington.edu
Michael D
MD
Weiss
Russell P
RP
Saneto
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