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Hermansky–Pudlak Syndrome

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Molecular Basis of Pulmonary Disease

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Abstract

Hermansky–Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by albinism and platelet dysfunction. A subset of HPS patients also develop highly penetrant pulmonary fibrosis, and some patients have a granulomatous colitis that shares features with Crohn’s disease. There are at least eight genetic loci associated with HPS in humans; mutations in each HPS gene result in defects in the biogenesis of lysosomes and lysosome-related intracellular organelles including melanosomes, platelet dense granules, and lamellar bodies. Pulmonary disease manifests as a restrictive disorder with insidious dyspnea on exertion, cough, and interstitial infiltrates and can progress to respiratory insufficiency and death by the fourth or fifth decade. Radiographically, HPS lung disease shares many features with idiopathic pulmonary fibrosis (IPF). Pulmonary fibrosis in HPS has a histologic appearance resembling usual interstitial pneumonia in several respects, but is also accompanied by hyperplastic, hypertrophic alveolar type II cells containing enlarged lamellar bodies, and lipid-filled, activated alveolar macrophages. Pigment deficiencies can be quite subtle. All pulmonary fibrosis patients with albinism and a bruising or bleeding diathesis should be screened for HPS. All patients with HPS should be screened for pulmonary involvement with pulmonary function tests and chest imaging. When indicated, bronchoscopy performed by the oral route should be considered to avoid nasal bleeding. Lung biopsy is frequently contraindicated because of bleeding complications and because diagnosis and prognosis can be determined without the procedure. Currently available approaches to treatment of HPS are limited, but include smoking cessation, vaccination against pulmonary infections, and prevention and management of bleeding complications. Pirfenidone and other targeted anti-inflammatory and antifibrotic agents warrant further study. Lung transplantation is an option for HPS patients with advanced pulmonary disease. The Hermansky–Pudlak Syndrome Network, Inc. (http://www.hpsnetwork.org), is a support organization available for patients with HPS.

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Authors and Affiliations

  1. Department of Pediatrics and Department of Internal Medicine, University of Cincinnati School of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Lisa R. Young MD

  2. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    William A. Gahl MD, PhD

Authors
  1. Lisa R. Young MD
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  2. William A. Gahl MD, PhD
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Editors and Affiliations

  1. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Francis X. McCormack

  2. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Ralph J. Panos

  3. Medical Center, Cincinnati Children's Hospital, Burnet Ave. 3333, Cincinnati, 45229, USA

    Bruce C. Trapnell

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Young, L.R., Gahl, W.A. (2010). Hermansky–Pudlak Syndrome. In: McCormack, F., Panos, R., Trapnell, B. (eds) Molecular Basis of Pulmonary Disease. Respiratory Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-384-4_8

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  • DOI: https://doi.org/10.1007/978-1-59745-384-4_8

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