Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism, a platelet storage pool defect and, in some patients, lysosomal accumulation of ceroid lipofuscin. Other manifestations include pulmonary fibrosis (often fatal in the fourth or fifth decade), chronic granulomatous colitis and, rarely, renal involvement or cardiomyopathy. There exist 10 different genes known to cause HPS, but only HPS-2 and HPS-10 have a basic defect whose mechanism is known, i.e., defective subunits of a coat protein, adaptor complex-3, responsible for intracellular vesicle formation. HPS-1 is a severe genetic type common in northwest Puerto Rico, and HPS-3 is a milder one seen in central Puerto Rico. HPS-4 resembles HPS-1 in severity; HPS-5 and HPS-6 resemble HPS-3 in severity. HPS-7, HPS-8, and HPS-9 are extremely rare and have not been fully characterized. The purpose of this protocol is to evaluate individuals with HPS, perform mutation analysis for known HPS-causing genes, search for variants in other genes responsible for HPS, and obtain specimens to analyze basic mechanisms of HPS.