The Journal of Pediatrics
Volume 154, Issue 4 , Pages 551-556 , April 2009

Clinical and Molecular Heterogeneity in Patients with the CblD Inborn Error of Cobalamin Metabolism

  • Isabelle R. Miousse, BSc

      Affiliations

    • Department of Human Genetics, McGill University Health Centre, Montreal, Quebec
    • ,
  • David Watkins, PhD

      Affiliations

    • Department of Human Genetics, McGill University Health Centre, Montreal, Quebec
    • Corresponding Author InformationReprint requests: David Watkins, PhD, Division of Medical Genetics, Room L3-319, McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada, H3G 1A4
    • ,
  • David Coelho, PhD

      Affiliations

    • Metabolic Unit, University Children's Hospital, Basel, Switzerland
    • ,
  • Tony Rupar, PhD

      Affiliations

    • Departments of Pediatrics, Biochemistry and the Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada
    • ,
  • Eric A. Crombez, MD

      Affiliations

    • Department of Pediatrics, University of California Los Angeles, Los Angeles
    • ,
  • Eric Vilain, MD

      Affiliations

    • Department of Pediatrics, University of California Los Angeles, Los Angeles
    • Department of Urology, University of California Los Angeles, Los Angeles
    • Department of Human Genetics, University of California Los Angeles, Los Angeles
    • ,
  • Jonathan A. Bernstein, MD, PhD

      Affiliations

    • Department of Pediatrics, Division of Genetics, Stanford University, Palo Alto, CA
    • ,
  • Tina Cowan, PhD

      Affiliations

    • Division of Pathology, Stanford University, Palo Alto, CA
    • ,
  • Christopher Lee-Messer, MD, PhD

      Affiliations

    • Division of Neurology, Stanford University, Palo Alto, CA
    • ,
  • Gregory M. Enns, MB, ChB

      Affiliations

    • Department of Pediatrics, Division of Genetics, Stanford University, Palo Alto, CA
    • ,
  • Brian Fowler, PhD

      Affiliations

    • Metabolic Unit, University Children's Hospital, Basel, Switzerland
    • ,
  • David S. Rosenblatt, MD

      Affiliations

    • Department of Human Genetics, McGill University Health Centre, Montreal, Quebec
    • Division of Medical Genetics, Department of Medicine, McGill University Health Centre, Montreal, Quebec

Received 21 May 2008 ,Revised 3 October 2008 ,Accepted 27 October 2008.

References 

  1. Rosenblatt DS, Fenton WA. Inherited disorders of folate and cobalamin transport and metabolism. In:  Scriver CR,  Beaudet AL,  Sly WS,  Valle D,  Childs B,  Kinzler KW, et al. editor. The metabolic and molecular bases of inherited disease. 8th ed.. New York: McGraw-Hill; 2001;p. 3897–3933
  2. Goodman SI, Moe PG, Hammond KB. Homocystinuria with methylmalonic aciduria: two cases in a sibship. Biochem Med. 1970;4:500–515
  3. Willard HF, Mellman IS, Rosenberg LE. Genetic complementation among inherited deficiencies of methylmalonyl-CoA mutase activity: evidence for a new class of human cobalamin mutant. Am J Hum Genet. 1978;30:1–13
  4. Suormala T, Baumgartner MR, Coelho D, Zavadakova P, Kozich V, Koch HG, et al. The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis. J Biol Chem. 2004;279:42742–42749
  5. Coelho D, Suormala T, Stucki M, Lerner-Ellis JP, Rosenblatt DS, Newbold RF, et al. Gene identification for the cblD defect of vitamin B12 metabolism. N Engl J Med. 2008;358:1454–1464
  6. Rosenblatt DS, Cooper BA, Pottier A, Lue-Shing H, Matiaszuk N, Grauer K. Altered vitamin B12 metabolism in fibroblasts from a patient with megaloblastic anemia and homocystinuria due to a new defect in methionine biosynthesis. J Clin Invest. 1984;74:2149–2156
  7. Jacobsen DW, Green R, Quadros EV, Montejano YD. Rapid analysis of cobalamin coenzymes and related corrinoid analogs by high-performance liquid chromatography. Anal Biochem. 1982;120:394–403
  8. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Invest Med. 1998;21:151–158
  9. Watkins D, Matiaszuk N, Rosenblatt DS. Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH). J Med Genet. 2000;37:510–513
  10. Baethmann M, Wendel U, Hoffmann GF, Gohlich-Ratmann G, Kleinlein B, Seiffert P, et al. Hydrocephalus internus in two patients with 5,10-methylenetetrahydrofolate reductase deficiency. Neuropediatrics. 2000;31:314–317
  11. Biancheri R, Cerone R, Schiaffino MC, Caruso U, Veneselli E, Perrone MV, et al. Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases. Neuropediatrics. 2001;32:14–22
  12. Andersson HC, Marble M, Shapira E. Long-term outcome in combined methylmalonic acidemia and homocystinuria (cblC). Genet Med. 1999;1:146–150

 The authors declare no conflicts of interest, real or perceived.

PII: S0022-3476(08)00954-2

doi: 10.1016/j.jpeds.2008.10.043

The Journal of Pediatrics
Volume 154, Issue 4 , Pages 551-556 , April 2009

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