Hermansky-Pudlak syndrome due to AP-3 deficiency

Hermansky-Pudlak syndrome due to AP-3 deficiency (also known as Hermansky-Pudlak syndrome type 2, or HPS-2) is a rare autosomal recessive disorder caused by mutations in the AP3B1 gene, which encodes the beta-3A subunit of the adaptor protein complex 3 (AP-3). AP-3 is involved in the trafficking of proteins to lysosomes and lysosome-related organelles. This subtype of Hermansky-Pudlak syndrome is distinguished from other forms by the prominent association with immunodeficiency in addition to the classic features of oculocutaneous albinism and bleeding diathesis. Patients with HPS-2 typically present in infancy or early childhood with hypopigmentation of the skin, hair, and eyes, nystagmus, reduced visual acuity, and a bleeding tendency due to platelet storage pool deficiency (absence of platelet dense granules). The immunodeficiency in HPS-2 is characterized by recurrent bacterial and viral infections, often respiratory, due to congenital neutropenia and impaired natural killer cell and cytotoxic T-lymphocyte function. Some patients may develop features resembling hemophagocytic lymphohistiocytosis (HLH). Pulmonary fibrosis, which is a hallmark of certain other HPS subtypes, is less commonly reported in HPS-2 but may occur. There is no cure for HPS-2. Management is supportive and multidisciplinary, including avoidance of sun exposure and use of sunscreen for skin protection, ophthalmologic care for visual impairment, desmopressin (DDAVP) or platelet transfusions for bleeding episodes, and prophylactic or therapeutic antibiotics for infections. Granulocyte colony-stimulating factor (G-CSF) may be used to manage neutropenia. Hematopoietic stem cell transplantation has been considered in severe cases with refractory immunodeficiency. Regular monitoring of lung function is recommended given the potential risk of pulmonary complications.

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