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Clinical and laboratory findings in referrals for mitochondrial DNA analysis
  1. SHINJI YANAI,
  2. PETER BAXTER,
  3. CHRIS RITTEY,
  4. PHILIP GUTHRIE,
  5. JAMES BONHAM,
  6. STUART TANNER
  1. Childrens Hospital
  2. Sheffeld S10 2TH, UK
  3. National Hospital for Neurology and Neurosurgery
  4. Queen Square, London WC1N 3BG, UK
    1. SIMON HEALES
    1. Childrens Hospital
    2. Sheffeld S10 2TH, UK
    3. National Hospital for Neurology and Neurosurgery
    4. Queen Square, London WC1N 3BG, UK

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      Editor,—Like Lamont and colleagues,1we have found that mtDNA mutations are uncommon, even among children seen at a neurogenetic referral centre. Only three of 135 children in North Trent who we investigated for suspected mitochondrial disorder between 1995 and 1998 had a positive finding (NARP T8993G, MELAS, and mtDNA depletion).

      However, it is likely that mtDNA studies alone will fail to diagnose many patients with mitochondrial disease. Additional investigative approaches including respiratory chain enzyme measurement can make a useful contribution to the identification of affected individuals.2 3 In our patients, two of the three with mtDNA abnormality and a further 15 without had reduced activity of one or more complexes. Maternal inheritance was more often associated with mtDNA abnormality (2 of 3 patients) than without (1 of 15). A lack of detected mtDNA abnormality was more frequently associated with parental consanguinity (5 of 15). Very young infants presenting with acute or subacute encephalopathy, who followed a severe course and died young, only occurred in the mtDNA negative group, particularly those with consanguinity. Epileptic seizures also only occurred in the group with biochemical abnormalities alone (6 of 15). Otherwise there was no difference in clinical features, either on presentation or follow up.

      We accept that the interpretation of reduced respiratory chain enzyme activity is difficult and a modest reduction in activity without other supporting evidence cannot be considered diagnostic. The positive predictive value of individual results will be modified by related information and hence the likelihood of the disease in a given patient. The results from 15 of our patients without mtDNA abnormality but with evidence of reduced respiratory chain enzyme activity and clinical features consistent with those described in mitochondrial disease suggests the need for an approach to investigation that includes respiratory chain enzyme measurement. Assessing the significance of any abnormal results may prove a more difficult problem!

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