Combined with previous reports of low-molecular-weight proteinuria in IGS patients [24,35-38,40] this constitutes a solid basis for classifying identified IGS causing mutations as either; 1) mutations affecting only receptor recognition of IF-B12 in the small intestine or 2) mutations of CUBN or AMN affecting the overall expression of cubilin on the cell surface resulting in both intestinal IF-B12 malabsorption and decreased proximal tubular reabsorption of cubilin ligands from the glomerular ultrafiltrate. Here, AMN is linked to megaloblastic anemia.