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Hermansky-Pudlak Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2000 Jul 24 [updated 2017 Oct 26].

Author information

1
Staff Scientist, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
2
Staff Clinician, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
3
Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

Excerpt

CLINICAL CHARACTERISTICS:

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.

DIAGNOSIS/TESTING:

The diagnosis of HPS is established by clinical findings of hypopigmentation of the skin and hair, characteristic eye findings, and demonstration of absent delta granules (dense bodies) on whole-mount electron microscopy of platelets. Identification of biallelic pathogenic variants in AP3B1, AP3D1, BLOC1S3, BLOC1S6, DTNBP1, HPS1,HPS3, HPS4, HPS5, or HPS6 confirms the diagnosis if clinical features are inconclusive.

MANAGEMENT:

Treatment of manifestations: Correction of refractive errors and use of low vision aids; humidifier to reduce frequency of epistaxis; oral contraceptives can limit the duration of menstrual periods; thrombin-soaked gelfoam for skin wounds with prolonged bleeding; DDAVP (1-desamino-8-D-arginine vasopressin) for wisdom tooth extraction and invasive procedures; platelet or red blood cell transfusions for surgery or protracted bleeding; supplemental oxygen and, ultimately, lung transplantation for severe pulmonary disease; steroids, other anti-inflammatory agents, and/or Remicade® for granulomatous colitis. Immunodeficiency, when present, is granulocyte colony-stimulating factor (G-CSF) responsive. Prevention of secondary complications: Protection of the skin from the sun; wearing a medical alert bracelet that explicitly describes the functional platelet defect; maximizing pulmonary function before development of pulmonary fibrosis by prompt treatment of pulmonary infections, immunizing with influenza and pneumococcal vaccines, and regular moderate exercise. Surveillance: Annual ophthalmologic examination; at least annual examination of the skin for solar keratoses (premalignant lesions), basal cell carcinoma, squamous cell carcinoma; annual pulmonary function testing in those older than age 20 years; routine history for symptoms of colitis (e.g., cramping, increased mucus in the stool, rectal bleeding). Agents/circumstances to avoid: Aspirin-containing products; activities that increase the risk of bleeding; cigarette smoke; direct sun exposure. Evaluation of relatives at risk: In rare families with the milder types (HPS3, HPS5, and HPS6-related HPS), the evaluation of apparently unaffected sibs may yield a positive diagnosis.

GENETIC COUNSELING:

HPS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible for those families in which the pathogenic variants have been identified.

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