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Neurological outcome of methylmalonic acidaemia
  1. P Nicolaides,
  2. J Leonard,
  3. R Surtees
  1. Institute of Child Health (UCLMS) and Great Ormond Street Hospital for Children NHS Trust, London WC1, UK
  1. Dr R A H Surtees, The Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK. email: R.Surtees{at}


OBJECTIVE To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study.

PATIENTS All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups.

RESULTS There was a significant difference between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant difference in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age.

CONCLUSIONS Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group.

  • Survival and neurological outcome in methylmalonic acidaemia is determined by the biochemical response to pharmacological doses of cobalamin and the age of onset of symptoms.

  • Early onset, cobalamin non-responsive patients have greater disease severity, a median survival of six years, and a poorer neurological and cognitive outcome.

  • Cobalamin non-responsive patients have an increased risk of developing new neurological symptoms and signs with age; these develop following episodes of acute metabolic decompensation.

  • methylmalonic acidaemia
  • cobalamin

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