J Neurol Neurosurg Psychiatry 79:725-728 doi:10.1136/jnnp.2007.133025
  • Short report

The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum

  1. C Thauvin-Robinet1,
  2. E Roze2,3,
  3. G Couvreur4,
  4. M-H Horellou5,
  5. F Sedel6,
  6. D Grabli6,
  7. G Bruneteau6,
  8. C Tonneti7,
  9. A Masurel-Paulet1,
  10. D Perennou8,
  11. T Moreau4,
  12. M Giroud4,
  13. H Ogier de Baulny9,
  14. S Giraudier7,
  15. L Faivre1
  1. 1
    Centre de Génétique, Hôpital d’Enfants, CHU, Dijon, France
  2. 2
    Service de Neurologie, Hôpital Saint Antoine, APHP, Paris, France
  3. 3
    CNRS UMR7102, Université Paris VI, Paris, France
  4. 4
    Service de Neurologie, Hôpital Général, CHU, Dijon, France
  5. 5
    Service d’Hématologie Biologique, Hôpital Hôtel-Dieu, APHP, Paris, France
  6. 6
    Fédération de Neurologie, CHU La Pitié-Salpêtrière, APHP, Paris, France
  7. 7
    Service d’Hématologie-Biologique, Hôpital Henri Mondor, Créteil, France
  8. 8
    Centre de Convalescence et de Rééducation, CHU, Dijon, France
  9. 9
    Service de Neuropédiatrie, Maladies Métaboliques, Hôpital Robert-Debré, APHP, Paris, France
  1. Dr C Thauvin-Robinet, Centre de Génétique, Hôpital d’Enfants, 10 Bd maréchal de Lattre de Tassigny, 21034 Dijon Cedex, France; christel.thauvin{at}
  • Received 22 August 2007
  • Revised 25 January 2008
  • Accepted 26 January 2008
  • Published Online First 1 February 2008


Background: Cobalamin C disease is the most common inborn error of cobalamin metabolism with an autosomal recessive mode of inheritance and mutations within the MMACHC gene. Clinical features, including systemic, haematological and neurological abnormalities, usually occur in the first year of life. Adolescent and adult onset presentations are rare.

Methods: We report on the clinical, molecular and imaging features in three patients aged 40, 42 and 42 years at the last follow-up. We examine these cases together with eight previously described cases to determine the clinical and molecular features of the disease in adults.

Results: Mean age at onset of clinical symptoms was 26 years; clinical features included predominant neurological disturbances and thromboembolic complications. White matter abnormalities on brain MRI were sometimes observed. Most patients (eight of nine patients investigated) were compound heterozygotes for the 271dupA mutation and a missense mutation. Intramuscular or intravenous hydroxycobalamin therapy stopped the progression of the disease and resulted in a better clinical outcome and favourable biological status in 7/9 treated cases, while the two untreated patients died quickly.

Conclusions: As cobalamine C disease and related disorders of homocysteine metabolism are treatable conditions, homocysteinaemia should be included in the investigations of patients with progressive neurological deterioration, unexplained psychiatric disturbances or recurrent thromboembolic events.


  • Competing interests: None.

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