Transcobalamin II deficiency at birth

Rene Ratschmann, Milen Minkov, Ana Kis, Christina Hung, Tony Rupar, Adolf Mühl, Brian Fowler, Ebba Nexo, Olaf A. Bodamer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited disorder of cobalamin transport that leads to intracellular cobalamin depletion with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase activities. Affected individuals may suffer from long-term neurological sequelae if therapy with intramuscular hydroxocobalamin is not initiated promptly. We report two sisters with complete absence of transcobalamin due to homozygosity for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop codon and non-functional protein. The older sister, now 4.5 years old, presented at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly declining clinical course. Prompt therapy with 1 mg hydroxocobalamin/day led to full recovery within days. Her now 1.5 year old sister was diagnosed shortly after birth and was started on hydroxocobalamin prior to onset of clinical symptoms. Interestingly, urinary methylmalonic acid excretion was increased significantly during the first days of life suggesting that functional cobalamin deficiency is present also during fetal life, although not giving rise to clinical symptoms until well after birth.

Original languageEnglish (US)
Pages (from-to)285-288
Number of pages4
JournalMolecular Genetics and Metabolism
Issue number3
StatePublished - Nov 2009


  • Cobalamin
  • Homocysteine
  • Methylmalonate
  • Transcobalamin
  • Vitamin B12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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