HPS3

HPS3 is a gene that encodes a subunit of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). This complex participates in the trafficking of pigment and other lysosome-related organelles to their proper locations, including melanosomes in skin and hair and dense bodies in platelets.

Mutations in HPS3 cause Hermansky-Pudlak syndrome type 3 (HPS-3), a rare autosomal recessive disorder. HPS-3 belongs to a group of conditions characterized by defects in the biogenesis of lysosome-related organelles, leading to combined pigmentary and connective tissue–related abnormalities.

Clinical features typically include oculocutaneous albinism with hypopigmented skin and hair, nystagmus, and reduced visual acuity. Bleeding tendency is common due to a deficiency of platelet dense bodies, which impairs platelet storage of hemostatic mediators. Some individuals may develop inflammatory or granulomatous colitis, and pulmonary involvement is variable across Hermansky-Pudlak types and not uniformly present in HPS-3.

Diagnosis relies on clinical features plus genetic testing confirming biallelic HPS3 mutations. Platelet electron microscopy can reveal reduced or absent dense granules, supporting the diagnosis.

Management is supportive and multidisciplinary, focusing on minimizing bleeding risk during procedures, ophthalmologic care for vision problems, and monitoring for gastrointestinal or other organ involvement. There is no cure for HPS-3, and prognosis varies with the extent of organ involvement and complications. Genetic counseling is recommended due to autosomal recessive inheritance.