Hermansky-Pudlak syndrome (HPS): A proposed block in glutathione peroxidase

Abstract

An unusual form of oculocutaneous albinism associated with a mild hemorrhagic diathesis and the accumulation of a ceroidlike pigment in the reticuloendothelial system was recognized by Hermansky and Pudlak in 1959. Examination of oral mucosal scrapings, urinary sediment, and bone marrow macrophages from patients with Hermansky-Pudlak syndrome (HPS) demonstrates that two forms of lipid accumulate in this disease. Many patients with this disorder have had spontaneous gingival hemorrhage, epistaxis, and prolonged bleeding following tooth extraction, delivery, and surgical procedures. Aspirin administered to such patients may enhance the bleeding diathesis. Analysis of the pigment defect shows that tyrosinase activity is present and pheomelanin pigment accumulates in melanocytes. Platelets lack an adequate storage pool of serotonin and the nonmetabolic nucleotides. A ceriodlike pigment accumulates in reticuloendothelial cells, urinary sediment, and buccal mucosa. The postulated enzymatic block accounting for this traid of signs is a defect in glutathione peroxidase.