Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption

Pediatr Nephrol. 2003 May;18(5):417-21. doi: 10.1007/s00467-003-1128-y. Epub 2003 Apr 5.


Selective vitamin B(12) malabsorption or Gräsbeck-Imerslund disease (megaloblastic anemia 1) is frequently accompanied by proteinuria. The malabsorption-proteinuric syndrome of Finnish patients is caused by a defect in the multiligand receptor cubilin. We studied the urinary proteins of control subjects and 13 adult patients with three defined cubilin mutations (FM1, FM2, FM3), all diagnosed during childhood and subsequently observed. The overall kidney function was unimpaired and did not deteriorate with time. The excretion of total protein and albumin, and to lesser extent of transferrin, immunoglobulin light chains, and alpha(1)- and beta(2)-microglobulins, was clearly elevated in 3 patients, mildly elevated in 3, and hardly or not at all increased in the rest. The urinary cobalamin-intrinsic factor receptor was low in 5 patients studied and lowest in the group with clear-cut proteinuria. The proteinuria was not of the classical glomerular or tubular type, but apparently due to the lack of cubilin function needed for tubular reabsorption of some, but not all, proteins of the primary urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Pernicious / genetics*
  • Anemia, Pernicious / metabolism
  • Anemia, Pernicious / urine
  • Female
  • Humans
  • Kidney Tubules / metabolism
  • Male
  • Middle Aged
  • Proteinuria / blood
  • Proteinuria / genetics*
  • Proteinuria / urine
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics*
  • Vitamin B 12 Deficiency / genetics*
  • Vitamin B 12 Deficiency / metabolism
  • Vitamin B 12 Deficiency / urine


  • Receptors, Cell Surface
  • intrinsic factor-cobalamin receptor