Deficient ferritin immunoreactivity in tissues from Niemann-Pick type C patients: Extension of findings to fetal tissues, H and L ferritin isoforms, but also one case of the rare Niemann-Pick C2 complementation group

Previous studies employing rabbit polyclonal anti-human liver ferritin have shown an absence of L ferritin immunoreactivity in liver and spleen tissue from patients with Niemann-Pick disease type C1 (NPC1). The great majority of NPC cases is caused by defects of the NPC1 gene, and a minority by thos e of another (NPC2). In this study using polyclonal and monoclonal antibodi es we show the deficiency of H and L ferritin isoforms in various NPC tissu es, including fetal NPC1, not previously described. In particular, evidence is provided for deficiency in H and L ferritins in tissues, except lung, f rom a patient with Niemann-Pick disease type Ca (NPC2). The present finding s indicate that H and L ferritins are deficient in both NPC types character ized by accumulation of unesterified cholesterol and additional metabolites in the endosomal/lysosomal system. We hypothesize that the lesions in NPC1 and NPC2 block the intracellular utilization not only of cholesterol, but also that of iron for the synthesis of cytosolic ferritin. (C) 2000 Academi c Press.