title: Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320).
abstract: BACKGROUND
  Plasma cobalamin is requested in order to diagnose cobalamin deficiency and low levels confirm a deficient state. Here, we present three family members with unexpected high levels of cobalamin.
  
  
  METHODS
  We included a patient referred for cobalamin measurement due to neurological symptoms, her son and her daughter. Mother and son both suffered from myotonic dystrophy type II, while the daughter tested negative for this disease. Blood samples were analyzed for cobalamin, haptocorrin, transcobalamin, holoTC, and sCD320. We employed gel filtration and antibody precipitation for further characterization. The protein coding region of the TCN2 gene, encoding transcobalamin, was sequenced.
  
  
  RESULTS
  The patient, her {son} and [daughter] all had cobalamin levels above the measurement range of the routine method employed (>1476 pmol/L). Total transcobalamin and (holoTC) were 5980 (1500), {5260 (2410)} and [5630 (1340)] pmol/L, which is well above the upper reference limits of 1500 (160) pmol/L. The sCD320 concentration was also well above the upper reference limit of 97 arb.u.: 1340, {1510} and [1090] arb.u. Haptocorrin levels were within the reference range and no signs of cobalamin deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both transcobalamin and part of sCD320.
  
  
  CONCLUSIONS
  The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark. ElkeHoff@rm.dk
authors.forename: Elke
authors.initials: E
authors.lastname: Hoffmann-Lücke
authors.forename: Johan F B
authors.initials: JF
authors.lastname: Arendt
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.forename: Gustav
authors.initials: G
authors.lastname: Mikkelsen
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics; D002850:Chromatography, Gel; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020967:Myotonic Disorders / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D009223:Myotonic Dystrophy; D009765:Obesity / Q000150:complications; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface; D017422:Sequence Analysis, DNA; D014155:Transcobalamins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C538894:CD320 protein, human; D011956:Receptors, Cell Surface; D014155:Transcobalamins; D014805:Vitamin B 12