Expanding the Spectrum of Polymerase Gamma-Related Ataxia.

Sir,

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.

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Conflicts of interest

There are no conflicts of interest.