In addition to decreased hair, ocular, and skin pigmentation, HPS patients suffer from bleeding diathesis, platelet deficiencies, and accumulation of ceroid material in lysosomes. Pigment can be found in large amounts in reticuloendothelial cells and in the walls of small blood vessels. Some of the same features are found in Chediak-Higashi syndrome (214500) which, however, has additional qualitative changes in leukocytes. HPS2 differs from other forms of HPS in having immunodeficiency and congenital neutropenia. Some patients, especially those with HPS1 and HPS4 mutations, have restrictive lung disease secondary to pulmonary fibrosis often causing symptoms in the third and fourth decades of life. Others have granulomatous colitis, kidney failure, and cardiomyopathy. Solar skin damage is a risk with actinic keratosis, nevi, lentigines and basal cell carcinoma seen in many patients.
Bleeding time is prolonged secondary to an impairment of the normal aggregation response of platelets. Easy bruising, epistaxis, prolonged bleeding during menstruation, after tooth extraction, and after minor surgical procedures are often reported. Platelets lack the normal number of 'dense bodies'. Coagulation factor activity and platelet counts are normal.
The amount of hair and skin pigmentation is highly variable. Some patients are so lightly pigmented that they are misdiagnosed as having tyrosinase-negative albinism while others have yellow to brown hair with irides blue to hazel. Some darkening of hair is common.