Hermansky-Pudlak syndrome due to BLOC-2 deficiency

Hermansky-Pudlak syndrome due to BLOC-2 deficiency encompasses subtypes HPS-3, HPS-5, and HPS-6 of Hermansky-Pudlak syndrome (HPS). These subtypes are caused by mutations in genes encoding components of the biogenesis of lysosome-related organelles complex 2 (BLOC-2), specifically HPS3, HPS5, and HPS6. BLOC-2 is involved in the trafficking of cargo to lysosome-related organelles, including melanosomes and platelet dense granules. Deficiency of this complex leads to the hallmark features of HPS: oculocutaneous albinism and a bleeding diathesis due to platelet storage pool deficiency. Patients with BLOC-2 deficiency typically present with hypopigmentation of the skin, hair, and eyes, along with visual impairment including nystagmus, reduced visual acuity, and iris transillumination. The bleeding tendency manifests as easy bruising, prolonged bleeding after surgery or dental procedures, epistaxis, and in women, heavy menstrual bleeding. Compared to other HPS subtypes (particularly HPS-1 and HPS-4, which are due to BLOC-3 deficiency), BLOC-2-related HPS is generally considered a milder form. Importantly, patients with BLOC-2 deficiency appear to have a significantly lower risk of developing pulmonary fibrosis and granulomatous colitis, which are the most serious and life-threatening complications seen in other HPS subtypes. There is no cure for BLOC-2-related HPS. Management is supportive and includes protection of the skin and eyes from sun damage, correction of refractive errors, use of low-vision aids, and precautions to manage bleeding risk. Desmopressin (DDAVP) may be used to reduce bleeding during surgical procedures. Platelet transfusions may be necessary for severe bleeding episodes. Regular ophthalmologic follow-up is recommended. Genetic counseling is important for affected families.

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