Sensori-neural hearing loss in Sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO): A Case Report

P Achar, BN Kumar


Department of ENT and Head Neck Surgery
Royal Albert Edward Infirmary, Wrightington, Wigan & Leigh NHS Trust, Wigan lane, Wigan, WN1 2NN

Abstract:
Objective: To report a case of bilateral sensorineural hearing loss in a patient with sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO).
Method: Case report and review of literature on mitochondrial disorders to facilitate understanding of the type of hearing loss.
Case report: We present a 37 year old lady diagnosed with SANDO, who was seen in the ENT department with a history of progressive hearing loss for 6 months. Audiogram showed bilateral trough shaped sensorineural hearing loss, dipping at 1 KHz. Earlier, this patient had presented to the neurology department with classical neurological signs of progressive sensory ataxia. Diagnosis of SANDO was confirmed by muscle biopsy and mitochondrial studies.
Conclusion: This is the first case report on SANDO documenting associated hearing loss in ENT literature. Further studies are required to explain the pattern of hearing loss in these patients
Key words:
SANDO neuropathy, sensorineural hearing loss, mitochondria, mutations

Introduction:
Polymerase gamma (POLG) gene has 3 functional domains and is mainly responsible for maintaining the integrity of mitochondrial DNA (mtDNA). Disorders related to mutations in this gene can present clinically with varying degrees of severity. SANDO neuropathy is one of the recently described disorders with POLG mutations. Since its description in 1997 1 by Fadic et al, there have been a few cases of SANDO being reported in the medical literature 2-7. It is characterised by a triad of sensory ataxic neuropathy, dysarthria with or without dysphagia and ophthalmoparesis. Patients usually present in the 3rd decade of life with ataxic gait; loss of distal proprioceptive and vibratory senses giving a positive Romberg’s test on examination; areflexia mainly involving lower limbs; and progressive external ophthalmoparesis. Dysarthria and dysphagia may or may not be present in the early stage. Diagnosis is made by electrophysiological tests and pathological demonstration of peripheral axonal neuropathy involving sensory nerves. Skeletal muscle biopsy characteristically shows myopathic changes with centralised nuclei and ragged red fibres. Molecular analysis demonstrates multiple mtDNA deletions which could range in size from 4.5 to 10kb 1. The clinical presentation would vary depending on the extent of involvement.

Case report:
A 37 year old lady, diagnosed with SANDO for 2 years was referred to ENT department in Wrightington, Wigan and Leigh NHS Trust with a 6 month history of progressive bilateral hearing loss. There was no associated history of tinnitus, dizziness or ear infections. She denied any previous acoustic trauma or head injury. Also there was no history of consumption of any ototoxic medications. On detailed ENT examination, she had normal looking ears. A pure tone audiogram showed bilateral symmetrical mild sensorineural hearing loss averaging 33 decibels (average over 0.5, 1, 2 and 3 KHz frequencies). Audiogram showed a classical trough shape with dip to 40db at 1 KHz frequency in both ears which is in keeping with the usual audiometric pattern of congenital hearing loss (fig I).

Fig I: Audiogram showing bilateral mild sensorineural hearing loss with characteristic trough at 1 KHz

In addition there was mild high frequency sensori neural hearing loss in both ears. She was recently diagnosed with an autosomal recessive sensory ganglionopathy for which she had been progressively symptomatic for 5 years. She was under the care of a neurologist, to whom she presented with a history of difficulty feeling the car pedals under her feet as a result of sensory loss, difficulty cycling due to reduced control over lower limb muscles and hip pain and loss of dexterity with hands e.g. difficulty buttoning shirts. Neurological examination revealed blunting of all sensory modalities in the lower limbs and absence of reflexes in lower limbs with positive Romberg’s test. Fundoscopy revealed marginally pale discs. She was diagnosed to have an autosomal recessive sensory neuropathy and underwent neurophysiological tests and muscle biopsy along with genetical and biochemical analysis. Her identical twin sister had a similar condition but had no associated hearing loss. A POLG1 mutation was found in both the siblings confirming the diagnosis of SANDO. She has been receiving physiotherapy and interventions from occupational therapy team to help her cope with her routine activities. Unfortunately this is a progressive disorder, with no treatment available as of today. We provided her with bilateral digital hearing aids to help augment her hearing.


Discussion:
Mitochondrial mutations have been found to be associated with a variety of multi-system disorders. Mitochondria are the primary ATP generating organelles in human cells. There have been studies demonstrating point mutations in mitochondria being the cause for hereditary susceptibility to aminoglycoside toxicity and also age related hearing loss 8. In the inner ear, the stria vascularis and dark cell regions are rich in mitochondria. A study on mice cochlea done by Someya S et al 9 demonstrates a model of how mitochondrial mutations can have an impact on cochlear function. Polymerase gamma gene infidelity causes accumulation of mitochondrial DNA mutations with resultant mitochondrial dysfunction and impaired energy metabolism. This induces apoptosis (cell death), with loss of cochlear hair cells and spiral ganglion neurons. This resultant damage to cytoskeletal structure of cochlea could be postulated to be the cause of age related hearing loss even in humans. Mutations in POLG gene of mitochondrial DNA have been identified in various mitochondrial disorders. Autosomal recessive Alper’s syndrome, autosomal dominant and recessive forms of progressive external ophthalmoplegia (PEO) and SANDO are a few of the examples of mitochondrial POLG mutational disorders. There have been only 2 cases of SANDO in literature 7, 10 which also describe associated hearing loss and they were reported in journals of neurology. However, there has been no mention on the characteristics of hearing loss in these patients and this condition is not well known in the ENT literature. Our case report documents the type and characteristic of the hearing loss noted in SANDO neuropathy. Although the patho-physiology of this pattern of sensorineural hearing loss is difficult to explain, it could very well be related to the mitochondrial mutation affecting the cochlea as well.


Conclusion:
In summary, SANDO neuropathy could present with sensorineural hearing loss as one of the presenting features. We do not know the progression of this hearing loss in view of the recent diagnosis of this entity; however these patients should be followed up with annual audiology to learn the characteristics and prognosis of sensorineural hearing loss.

References:

  1. Fadic R, Russell JA, Vedanarayanan VV, Lehar M, Kuncl RW and Johns DR. Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease. Neurology 1997; 49 (1): 239–245.
  2. Van Goethem G, Martin JJ, Dermaut B, et al. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord 2003; 13 (2): 133–142.
  3. Van Goethem G, Luoma P, Rantamaki M, et al. POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology 2004; 63 (7): 1251–1257
  4. Winterthun S, Ferrari G, He L, et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations, Neurology 2005; 64 (7): 1204–1208
  5. Hudson G, Deschauer M, Busse K, Zierz S and Chinnery PF. Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism, Neurology 2005; 64 (2): 371–373
  6. Gago MF, Rosas MJ, Guimaraes J, et al. SANDO: Two novel mutations in POLG1 gene. Neuromuscular disorders. 2006; 16(8): 507-509
  7. Milone M, Brunetti-Pierre N, Tang L, et al. Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations. Neuromuscular disorders. 2008; 18(8): 626-632
  8. Cortopassi G, Hutchin T. A molecular and cellular hypothesis for aminoglycoside-induced deafness. Hear Res. 1994; 78: 27–30
  9. Someya S, Yamasoba T, Kujoth GC, et al. The role of mtDNA mutations in the pathogenesis of age related hearing loss in mice carrying a mutator DNA polymerase. Neurobiology of ageing. 2008; 29(7): 1080-1092
  10. Mancuso M, Filosto M, Bellan M, et al. POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia and deafness. Neurology 2004; 62: 316-318

 

Summary:
SANDO is a mitochondrial mutation disorder with a characteristic triad of Sensory Ataxic Neuropathy, Dysarthria with or without dysphagia and Ophthalmopareisis.
Being a mitochondrial DNA mutation, patients can also develop sensorineural hearing loss.
This case report highlights the characteristic of sensorineural hearing loss noted in SANDO. 2 previous reports in literature have mentioned associated hearing loss, but there is no description of the type of hearing loss and no such report in ENT literature.