A Case of Childhood Onset of Extended Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis Phenotype with Pathogenic Polymerase Gamma Variation

Abstract

Background: Ataxia neuropathy spectrum, including sensory ataxia neuropathy, dysarthria, and ophthalmoparesis (SANDO), is a part of polymerase gamma (POLG) gene-related disorder, a heterogeneous group of mitochondrial disorders. Childhood onset of the SANDO phenotype is rare, and we describe such a case here, probably the first from India. Clinical Description: A 17-year-old girl presented with progressive gait abnormality since 5 years of age, later associated with ptosis and seizures. On examination, she had atrophy of distal small muscles and absent tendon reflexes in addition to ataxia and ptosis. Differentials for a neurodegenerative disorder with cognitive sparing and ophthalmoplegia were suspected. Management: Investigations revealed a mild elevation in serum lactate, transaminases, and creatine phosphokinase, with abnormal neurophysiology showing primary muscle disease with symmetrical sensorimotor polyneuropathy, and a normal neuroimaging. Gene sequencing analysis for the mitochondrial disorder was done, which revealed a pathogenic variation in the POLG gene. The child was kept on supportive management, including antiepileptics. Conclusion: This case shows that the SANDO phenotype of POLG-related disorders, classically seen in adults, may rarely be seen in children. Our case highlights the fact that although many of the progressive neurodegenerative disorders have a nonspecific clinical presentation, biomarkers, and neurophysiologic abnormalities, a few important phenotypic clues and awareness of POLG-related disorders may enable a pediatrician to order focused genetic testing to delineate the etiology.