Hermansky-Pudlak syndrome

HPS · oculocutaneous albinism with platelet storage pool deficiency

Hermansky-Pudlak syndrome (HPS) is a group of autosomal recessive disorders of lysosome-related organelle biogenesis. Patients have oculocutaneous albinism, a platelet δ-storage-pool deficiency causing prolonged bleeding, and — in several subtypes — pulmonary fibrosis, granulomatous colitis or immunodeficiency. Cutaneous malignancy risk is comparable to that of oculocutaneous albinism. Pulmonary fibrosis is the leading cause of death in HPS-1 and HPS-4.

CurrentLast reviewed 16 May 2026

Genetics

Autosomal recessive. At least 11 genes (HPS1 to HPS11) encode subunits of BLOC-1, BLOC-2, BLOC-3 and AP-3 — protein complexes that traffic cargo to lysosome-related organelles (melanosomes, platelet dense granules, lamellar bodies in pneumocytes).
HPS-1 — most common in Puerto Rico (founder mutation); pulmonary fibrosis common.
HPS-2 and HPS-10 — AP-3 mutations; immunodeficiency phenotype.
HPS-4 — pulmonary fibrosis.

Clinical features

Oculocutaneous albinism — variable; nystagmus, reduced visual acuity, iris transillumination, foveal hypoplasia. Skin photoprotection lifelong.
Bleeding diathesis — platelet δ-granule deficiency; epistaxis, easy bruising, post-partum and post-operative haemorrhage; normal platelet count but absent dense bodies on electron microscopy.
Pulmonary fibrosis — onset in 3rd-4th decade in HPS-1 / HPS-4; restrictive lung disease; major cause of mortality.
Granulomatous colitis — Crohn-like, especially HPS-1.
Immunodeficiency — recurrent infections in HPS-2 / HPS-10.

Cutaneous cancer risk

Cutaneous squamous cell carcinoma and basal cell carcinoma — elevated, similar to other oculocutaneous albinism syndromes; risk concentrated on sun-exposed sites.
Cutaneous melanoma can occur (including amelanotic); biopsy unusual pigmented lesions and any rapidly growing nodule.
Long-term photoprotection: high-SPF sunscreen, protective clothing, sun-avoidance counselling from childhood.

Diagnosis

Clinical features + family history.
Electron microscopy of platelets — absent dense bodies is pathognomonic (≤1 dense body per platelet).
Genetic panel — HPS gene multi-gene panel (HPS1-HPS11).
HRCT chest for pulmonary fibrosis surveillance in HPS-1 / HPS-4.

Practical points for skin / surgical care

Pre-operative haematology review for any planned procedure — desmopressin (DDAVP) for minor procedures; platelet transfusion for major surgery.
Avoid aspirin, NSAIDs and other antiplatelet agents.
Plan for additional bleeding management at Mohs / WLE; pressure dressings; topical haemostats (Floseal, Surgicel).
Annual skin examination from adolescence; total-body photography for melanoma surveillance.
Refer for pulmonary, ophthalmic and clinical genetics input.

References

Huizing M et al. Hermansky-Pudlak syndrome: mosaic for an albinism mutation. Mol Genet Metab. 2020;131:1-7.

Wei AH, Li W. Hermansky-Pudlak syndrome: pigmentary and non-pigmentary defects and their pathogenesis. Pigment Cell Melanoma Res. 2013;26:176-192.

Vicary GW et al. Pulmonary fibrosis in Hermansky-Pudlak syndrome. Ann Am Thorac Soc. 2016;13:1839-1846.

Gahl WA et al. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998;338:1258-1264.