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European Journal of Pediatrics

, Volume 167, Issue 6, pp 671–675 | Cite as

Imerslund-Gräsbeck syndrome in a 15-year-old German girl caused by compound heterozygous mutations in CUBN

  • Fabian H. HauckEmail author
  • Stephan M. Tanner
  • Jobst Henker
  • Martin W. Laass
Original Paper

Abstract

Imerslund-Gräsbeck syndrome (IGS) is a recessive disorder of intestinal cobalamin (Cbl) absorption and renal tubular protein reabsorption sometimes accompanied by urinary tract malformation. Mutations in the cubilin (CUBN) and amnionless (AMN) genes have been described as causal defects. CUBN and AMN proteins form the cubam complex that functions as the receptor for the intrinsic factor-Cbl (IF-Cbl) complex in the ileum and for proteins found in the primary urine in the kidney. We report the case of a 15-year-old German girl who presented with megaloblastic anaemia and funicular myelosis due to Cbl-deficiency and selective proteinuria. We clinically diagnosed- and for the first time in a patient of German ancestry-genetically confirmed IGS by detecting a compound heterozygous gene deletion and missense mutation in the CUBN gene. In conclusion IGS should be considered in paediatric patients presenting with symptoms like megaloblastic anaemia, funicular myelosis and benign proteinuria. Diagnosis should be confirmed genetically to avoid further invasive diagnostics, administer proper lifelong treatment and offer genetic counselling.

Keywords

Cobalamin malabsorption Megaloblastic anaemia Proteinuria Funicular myelosis Intrinsic factor deficiency 

Abbreviations

AMN

amnionless gene

Cbl

cobalamin (vitamin B12)

CUBN

cubilin gene

EGF

epidermal growth factor

GIF

gastric intrinsic factor gene

IF

intrinsic factor

IFD

intrinsic factor deficiency

IGS

Imerslund-Gräsbeck syndrome

MGA

megaloblastic anaemia

Notes

Acknowledgements

We thank Dr. med. Ilona Zapf as primary outpatient physician, Zhongyuan Li, and James D. Perko for technical assistance in the laboratory.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Fabian H. Hauck
    • 1
    • 3
    Email author
  • Stephan M. Tanner
    • 2
  • Jobst Henker
    • 1
  • Martin W. Laass
    • 1
  1. 1.Department of PaediatricsUniversity Hospital Carl Gustav Carus at the Technical University DresdenDresdenGermany
  2. 2.Human Cancer Genetics ProgramThe Ohio State UniversityColumbusUSA
  3. 3.Klinik und Poliklinik für Kinder- und JugendmedizinUniversitätsklinikum Carl Gustav CarusDresdenGermany

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