In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with
hemochromatosis of unknown etiology,
Wilson disease of primary
copper toxicosis, and the black liver of
Dubin-Johnson syndrome. Three patients with middle-age onset
hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with
Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for
copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of
ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and
iron complex. Six patients with
Dubin-Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices.