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Year : 2019  |  Volume : 22  |  Issue : 4  |  Page : 525

Expanding the spectrum of polymerase gamma-related ataxia

Department of Neurology, Kansas University Medical Center, Kansas City, KS, USA

Date of Submission02-Jan-2019
Date of Acceptance16-Jan-2019
Date of Web Publication25-Oct-2019

Correspondence Address:
Dr. Harsh Vardhan Gupta
Department of Neurology, Kansas University Medical Center, Kansas City, KS
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_3_19

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How to cite this article:
Gupta HV, Karlowski K, Burka T. Expanding the spectrum of polymerase gamma-related ataxia. Ann Indian Acad Neurol 2019;22:525

How to cite this URL:
Gupta HV, Karlowski K, Burka T. Expanding the spectrum of polymerase gamma-related ataxia. Ann Indian Acad Neurol [serial online] 2019 [cited 2020 Sep 26];22:525. Available from:


A wide spectrum of neurological signs and symptoms can be seen in polymerase gamma (POLG)-related disorders.[1] Due to overlapping clinical features, the diagnosis is not possible based on clinical features alone, and genetic testing is necessary.[1]

A 61-year-old female was referred to our clinic for the evaluation of imbalance and falls. She reported clumsiness in her 20s and required the use of a cane for walking. Her father had similar problems and died in his 70 s, and her daughter was developing similar symptoms. On neurological examination, her cranial nerves were intact except for bilateral hearing loss. There was end-gaze nystagmus bilaterally, but vertical nystagmus was not seen. The motor examination showed 5/5 strength throughout with normal muscle bulk. Reflexes were absent at the ankles bilaterally without Hoffman's or ankle clonus. Sensory testing showed impaired pinprick below the ankles, and vibration was around 9 s in the distal lower extremities. Coordination showed dysmetria on finger-nose-finger testing and finger chase which was prominent on the right than the left. She was unable to stand and walk tandem. There was a rest tremor in the right upper extremity. A postural, action, and intention tremor was seen in the bilateral upper extremities (right >left). The plantar response was flexor bilaterally [Video 1]. Electromyograpvidhy-nerve conduction study was normal, magnetic resonance imaging (MRI) brain did not show cerebellar atrophy, and echocardiogram did not show cardiomyopathy. Genetic testing was performed with Athena Diagnostics ® which looks for 11 repeat expansion tests, and 33 genes are sequenced. The test identified a pathogenic mutation in POLG gene (c.2542G>A) inherited in an autosomal recessive manner. A similar pathogenic mutation has been described in a patient with Alpers' syndrome.[2]

Mutation in POLG gene causing ataxia was identified in 27 patients from 15 Finnish families.[3] Nerve conduction study was performed in all but four patients which showed evidence of neuropathy associated with a decrease in deep tendon reflexes and vibration.[3] Interestingly, all patients had some form of oculomotor abnormality such as restricted eye movements, nystagmus, or ptosis.[3] Imaging abnormalities such as white matter changes in the cerebellum, thalamic lesion, or cerebellar atrophy were seen in majority of the patients.[3] In another study, three families with ataxia due to POLG mutation were described where the initial symptom was headache or epilepsy except in one patient and neuropathy was present in all the subjects.[4] Movement disorders such as myoclonus or tremor can also be seen with POLG mutation.[1] Similar to our case, other conditions where cerebellar atrophy can also be absent include Friedreich's ataxia, abetalipoproteinemia, ataxia with Vitamin E deficiency, Refsum's disease, cerebrotendinous xanthomatosis, and Niemann-Pick Type C disease.[5] Refsum's disease can also cause deafness and neuropathy besides ataxia which can mimic the phenotype of POLG ataxia.[5] Our case expands the phenotypic spectrum of POLG-related disorders as ataxia is seen in the absence of myopathy, neuropathy, myoclonus, epilepsy, and ophthalmoplegia. MRI brain did not show any changes or cerebellar atrophy and nerve conduction study was normal as well.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Cohen BH, Chinnery PF, Copeland WC. POLG-related Disorders. In: GeneReviews™. Available from: [Last accessed on 2018 Nov 11].  Back to cited text no. 1
Simon M, Chang RC, Bali DS, Wong LJ, Peng Y, Abdenur JE, et al. Abnormalities in glycogen metabolism in a patient with Alpers' syndrome presenting with hypoglycemia. JIMD Rep 2014;14:29-35.  Back to cited text no. 2
Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma PT, Rantamaki M, et al. Mitochondrial DNA polymerase W748S mutation: A common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet 2005;77:430-41.  Back to cited text no. 3
Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM, et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology 2005;64:1204-8.  Back to cited text no. 4
Anheim M, Tranchant C, Koenig M. The autosomal recessive cerebellar ataxias. N Engl J Med 2012;366:636-46.  Back to cited text no. 5


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