European Journal of Pediatrics

, Volume 163, Issue 4–5, pp 196–201

Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature

  • G. Christoph Korenke
  • Donald H. Hunneman
  • Stefan Eber
  • Folker Hanefeld
Original Paper


Vitamin B12 deficiency is one of the major causes of megaloblastic anaemia with or without neurological symptoms. We report on a patient manifesting acute encephalopathy, epilepsy, microcephaly and megaloblastic anaemia at the age of 4 months. Vitamin B12 deficiency in the patient was due to subclinical pernicious anaemia of the mother who exhibited neither haematological nor neurological symptoms. Mother and child both had elevated methylmalonic acid in their urine which is a sensitive parameter of vitamin B12 deficiency. Vitamin B12 therapy resulted in arrest of convulsions within 24 h. There were no further seizures although the patient showed moderate mental retardation at the age of 7 years but a normal head circumference. Long-term MRI follow-up, performed at the age of 7 years, showed moderate enlargement of the ventricles with reduction of myelin and hypoplasia of the corpus callosum. Conclusion:vitamin B12 deficiency due to maternal pernicious anaemia should always be considered in the differential diagnosis of neurological symptoms in infants and especially in combination with megaloblastic anaemia. Since the age of onset and the duration of neurological symptoms may contribute to the development of long-term symptoms, early diagnosis and treatment is important for vitamin B12 deficient children.


Epilepsy Megaloblastic anaemia Methylmalonic acid Pernicious anaemia Vitamin B12 deficiency 


  1. 1.
    Allen LH (1994) Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol 352: 173–186PubMedGoogle Scholar
  2. 2.
    Frenkel E (1973) Abnormal fatty acid metabolism in peripheral nerve of patients with pernicious anaemia. J Clin Invest 52: 1237–1245PubMedGoogle Scholar
  3. 3.
    Frery N, Huel G, Leroy M, Moreau T, Savard R, Blot P, Lellouch J (1992) Vitamin B12 among parturients and their newborns and its relationship with birthweight. Eur J Obstet Gynecol Reprod Biol 45: 155–163PubMedGoogle Scholar
  4. 4.
    Giugliani ER, Jorge SM, Goncalves AL (1985) Serum vitamin B12 levels in parturients, in the intervillous space of the placenta and in full-term newborns and their interrelationships with folate levels. Am J Clin Nutr 41: 330–335PubMedGoogle Scholar
  5. 5.
    Graham SM, Arvela OM, Wise GA (1992) Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 121: 710–714PubMedGoogle Scholar
  6. 6.
    Hoey H, Linnell JC, Oberholzer VG, Laurence BM (1982) Vitamin B12 deficiency in a breast fed infant of a mother with pernicious anaemia. J Roy Soc Med 75: 656–658Google Scholar
  7. 7.
    Jadhav M, Webb J, Vaishnava S, Baker S (1962) Vitamin B12 deficiency in Indian infants. Lancet 2: 903–907CrossRefPubMedGoogle Scholar
  8. 8.
    Johnson PR, Roloff JS (1982) Vitamin B12 deficiency in an infant strictly breast-fed by a mother with latent pernicious anaemia. J Pediatr 100: 917–919PubMedGoogle Scholar
  9. 9.
    Kuehne T, Bubl R, Baumgartner R (1991) Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency. Eur J Pediatr 150: 205–208PubMedGoogle Scholar
  10. 10.
    Lampkin BC, Shore NA, Chadwick D (1966) Megaloblastic anemia of infancy secondary to maternal pernicious anemia. N Engl J Med 274: 1168–1171PubMedGoogle Scholar
  11. 11.
    Lövblad K, Ramelli G, Remonda L, Nirkko AC, Ozdoba C, Schroth G (1997) Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings. Pediatr Radiol 27: 155–158CrossRefPubMedGoogle Scholar
  12. 12.
    Lundgren J, Blennow G (1999) Vitamin B12 deficiency may cause benign familial infantile convulsions: a case report. Acta Paediatr 88: 1158–1160CrossRefPubMedGoogle Scholar
  13. 13.
    Mattson MP, Shea TB (2003) Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26: 137–146CrossRefPubMedGoogle Scholar
  14. 14.
    McPhee AJ, Davidson GP, Leahy M, Beare T (1988) Vitamin B12 deficiency in a breast fed infant. Arch Dis Child 63: 921–923PubMedGoogle Scholar
  15. 15.
    Michaud JL, Lemieux B, Ogier H, Lambert MA (1992) Nutritional vitamin B12 deficiency: two cases detected by routine newborn urinary screening. Eur J Pediatr 151: 218–220PubMedGoogle Scholar
  16. 16.
    Monagle PT, Tauro GP (1997) Infantile megaloblastosis secondary to maternal vitamin B12 deficiency. Clin Lab Haematol 19: 23–25CrossRefPubMedGoogle Scholar
  17. 17.
    Mudd SH, Poole JR (1975) Labile methyl balances for normal humans on various dietary regimens. Metabolism 24: 721–735PubMedGoogle Scholar
  18. 18.
    Ogier de Baulny H, Gerard M, Saudubray JM, Zittoun J (1998) Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr 157[Suppl 2]: S77–S83Google Scholar
  19. 19.
    Oh R, Brown DL (2003) Vitamin B12 deficiency. Am Fam Physician 67:979–986PubMedGoogle Scholar
  20. 20.
    Pearson AGM, Turner AJ (1975) Folate dependent 1-carbon transfer to biogenic amines mediated by methylenetetrahydrofolate reductase. Nature 258: 173–174PubMedGoogle Scholar
  21. 21.
    Rosenblatt DS, Whitehead VM (1999) Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol 36: 19–34Google Scholar
  22. 22.
    von Schenck U, Bender-Götze C, Koletzko B (1997) Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy. Arch Dis Child 77: 137–139PubMedGoogle Scholar
  23. 23.
    Schulze A (2003) Creatine deficiency syndromes. Mol Cell Biochem 244: 143–150CrossRefPubMedGoogle Scholar
  24. 24.
    Specker BL, Miller D, Norman EJ, Greene H, Hayes KC (1988) Increased urinary methylmalonic acid excretion in breast-fed infants of vegetarian mothers and identification of an acceptable dietary source of vitamin B-12. Am J Clin Nutr 47: 89–92PubMedGoogle Scholar
  25. 25.
    Specker BL, Black A, Allen L, Morrow F (1990) Vitamin B-12: low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduria in their infants. Am J Clin Nutr 52: 1073–1076PubMedGoogle Scholar
  26. 26.
    Stollhoff K, Schulte FJ (1987) Vitamin B12 and brain development. Eur J Pediatr 146: 201–205PubMedGoogle Scholar
  27. 27.
    Willoughby MLN (1977) Vitamin B12 metabolism and deficiency. In: Willoughby MLN (ed) Paediatric haematology. Churchill Livingstone, Edinburgh, pp 35–42Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • G. Christoph Korenke
    • 1
    • 3
  • Donald H. Hunneman
    • 1
  • Stefan Eber
    • 2
  • Folker Hanefeld
    • 1
  1. 1.Department of Paediatrics and NeuropaediatricsUniversity of Göttingen Germany
  2. 2.Department of Paediatric Immunology, Haematology, Oncology, BMT University Children’s HospitalZürich Switzerland
  3. 3.Klinik für NeuropädiatrieZentrum Kinder- und Jugendmedizin, Klinikum OldenburgOldenburg Germany

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