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

Eur J Pediatr 167(6):671-5 (2008) PMID 17668238

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.