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Cochlear implantation in a profoundly deaf patient with MELAS syndrome
  1. A R Sinnathuray1,
  2. V Raut1,
  3. J G Toner1,
  4. A Magee2
  1. 1Department of Otolaryngology, Belfast City Hospital, Belfast, UK
  2. 2Department of Medical Genetics, Queen's University, Belfast at the Belfast City Hospital
  1. Correspondence to:
 Mr J G Toner, Director, Regional Cochlear Implant Centre, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, UK;
  1. J Graham3
  1. 3UCL Cochlear Implant Unit, Royal National Throat, Nose & Ear Hospital, 330–332 Gray's Inn Road, London WC1X 8DA, UK

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    In response to the article “Cochlear implantation in a profoundly deaf patient with MELAS syndrome” (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes),1 we feel concerned that this patient may have a different diagnosis. This woman who received a cochlear implant is described as having the MELAS syndrome, in both the title and the text, when perhaps she has the less severe maternally inherited diabetes mellitus with deafness (MIDD) syndrome.

    She has the A3243G point mitochondrial DNA (mtDNA) mutation associated with insulin dependent diabetes mellitus, congenital cataracts, short stature, leg weakness, fatigue, and sensorineural hearing loss (SNHL), with no encephalopathy or strokes. The age of onset of SNHL was 22 years, with a slow deterioration to right profound SNHL at the age of 29 years, and bilateral profound SNHL and tinnitus at the age of 30 years. Caloric testing and computed tomography of her temporal bones were both normal. Her mother suffered from diabetes, glaucoma, and a lesser degree of SNHL, and a sister has profound SNHL and mental retardation.

    MELAS is a multisystem disorder with a wide variety of possible clinical features. Among these multiple features, the diagnostic criteria for MELAS are as follows 2:

    • Stroke-like episodes before age 40 years;

    • Encephalopathy (seizures, dementia, or both);

    • Mitochondrial myopathy (lactic acidosis, ragged red muscle fibres, or both);

    • Two of the following three: normal early psychomotor development, recurrent headache, recurrent vomiting.

    Now these clinical findings can be confirmed with a positive molecular genetic test for mtDNA mutations.3 The A3243G mutation in the mitochondrial tRNALeu(UUR) gene, MTTL1, causes MELAS and is responsible for MELAS in approximately 80% of patients.

    MIDD has a narrower phenotype of bilateral, progressive, symmetrical SNHL, generally preceding diabetes mellitus (ranging from abnormal glucose tolerance to insulin dependent diabetes mellitus) and occurs in adulthood, on a background of maternal inheritance. Sporadic occurrence has been noted.4 It is associated with short stature and can be expressed as type 1-like or type 2-like diabetes.5 The A3243G transition mutation has been identified as the cause of MIDD in 60% of cases.

    In patients with mtDNA disease, affected cells and tissues tend to harbour mixtures of mutant and wildtype mtDNA in different proportions. This is called “heteroplasmy”, as opposed to “homoplasmy”, where only one type is present. It is hypothesised that phenotypic expression of mtDNA pathology may occur when heteroplasmy within an organ reaches a certain level. This concept is known as the “threshold effect”. The severity of the phenotype is thought to correlate with the degree of heteroplasmy in different tissues. Interestingly, both syndromes, MELAS and MIDD, can be found in a single pedigree with the A3243G mutation. The A3243G mutation is also associated with Kearns-Sayre syndrome. Assuming that all patients with the A3243G mutation have the MELAS syndrome leads to an incorrect diagnosis, with significant implications for patient counselling. A diagnosis of MELAS implies that the patient has developed stroke-like episodes or encephalopathy.

    As more people with SNHL become genotyped and the identification of the true prevalence of mitochondrial SNHL becomes more obvious, a database of already successfully treated patients by cochlear implantation will be useful for quantitative analyses of performances of these patients with cochlear implants. Here also, the correct label must be assigned to patients.

    More information on mitochondrial SNHL can be obtained on the Hereditary Hearing loss Homepage on


    Author's reply

    We are grateful to Dr Sinnathuray and colleagues for their very useful comments on the precise diagnosis of our patient's condition. We agree entirely with the comment that the A3243G mutation also occurs in maternally inherited diabetes mellitus with deafness (MIDD). In our patient the original diagnosis was made by a clinical geneticist in 1994 and therefore, in a rapidly changing field, greater precision in diagnosis might have been possible with a further genetics consultation at a later date. We should point out that this article was originally submitted in November 2000 and this, also, may have contributed to the diagnosis of MELAS syndrome rather than MIDD syndrome. We are most grateful to Dr Sinnathuray and colleagues for their useful comments.