title: Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption.
abstract: 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.
authors.affiliation: The Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
authors.forename: Virve
authors.initials: V
authors.lastname: Wahlstedt-Fröberg
authors.forename: Tom
authors.initials: T
authors.lastname: Pettersson
authors.forename: Maria
authors.initials: M
authors.lastname: Aminoff
authors.forename: Benoît
authors.initials: B
authors.lastname: Dugué
authors.forename: Ralph
authors.initials: R
authors.lastname: Gräsbeck
mesh_terms: D000328:Adult; D000752:Anemia, Pernicious / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000235:genetics* / Q000652:urine; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D014806:Vitamin B 12 Deficiency / Q000235:genetics* / Q000378:metabolism / Q000652:urine
chemical_list: D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor