title: Transcobalamin II deficiency at birth.
abstract: 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 1mg 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.
authors: Department of General Paediatrics and Neonatology, University Children's Hospital, Vienna, Austria.
authors: Rene
authors: R
authors: Ratschmann
authors: Milen
authors: M
authors: Minkov
authors: Ana
authors: A
authors: Kis
authors: Christina
authors: C
authors: Hung
authors: Tony
authors: T
authors: Rupar
authors: Adolf
authors: A
authors: Mühl
authors: Brian
authors: B
authors: Fowler
authors: Ebba
authors: E
authors: Nexo
authors: Olaf A
authors: OA
authors: Bodamer
mesh_terms: D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008764:Methylmalonic Acid / Q000652:urine; D010198:Pancytopenia / Q000378:metabolism / Q000473:pathology; D014155:Transcobalamins / Q000172:deficiency* / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014155:Transcobalamins; D008764:Methylmalonic Acid; D014805:Vitamin B 12