Case reportSANDO: Two novel mutations in POLG1 gene
Introduction
The clinical triad of sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO) was first proposed in 1997 as an unique mitochondrial phenotype associated with multiple mtDNA deletions [1]. This clinical picture was initially described in four sporadic unrelated patients with adult onset of severe sensory ataxic neuropathy in association with dysarthria and chronic progressive external ophthalmoplegia. The patients had ataxic gait, loss of distal proprioception and vibration, areflexia on the lower limbs, positive Romberg sign and electrophysiologic and pathologic evidence of a peripheral axonal neuropathy. Skeletal muscle biopsy showed myopathic changes with centralized nuclei and ragged-red fibers. Molecular analysis in muscle and peripheral nerve detected multiple mitochondrial DNA (mtDNA) deletions but the genes responsible were not further investigated. More recently, mutations in the POLG1 (DNA polymerase-γA) [2], [3], [4] and the C10orf2 gene (Twinkle helicase) [5] genes have been described (Table 1).
Section snippets
Clinical case
A 44-year-old man presented at age 39 progressive bilateral ptosis, unsteadiness gait and muscle weakness with difficulty in dressing and lifting objects. Three years later he noticed dysphagia and diplopia and sought medical advice. Neurological examination revealed droopy eyes which worsened after repeated eye movements and external ophthalmoparesis with diplopia on horizontal gaze. The patient also presented fluctuant dysarthria and dysphagia which worsened at the end of the day. There was
Discussion
The clinical phenotype in our patient fulfills the clinical triad of SANDO which occurred most likely in the absence of a family history. Previous reports suggests that SANDO is either sporadic [1] or inherited as an autosomal recessive [2] or dominant trait [5]. As the first described patients with SANDO [1], NCS and nerve biopsy suggests a sensory ganglionopathy with presumed preferential involvement of the dorsal root ganglia with axonal degeneration of the large-diameter sensory axons.
The
Acknowledgements
The author thanks Dr. Carolina Garrett and Dr. Castro-Neves for article revision, and Dr. Fernando Silveira for his contribution on neurophysiology study.
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