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Hermansky–Pudlak Syndrome

  • Lisa R. Young
  • William A. Gahl
Chapter
Part of the Respiratory Medicine book series (RM)

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.

Keywords

pulmonary fibrosis interstitial lung disease genetic basis of disease alveolar macrophage alveolar type II cell 

References

  1. 1.
    Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: Report of two cases with histochemical studies. Blood 1959;14:162–9.PubMedGoogle Scholar
  2. 2.
    Wildenberg SC, Oetting WS, Almodovar C, Krumwiede M, White JG, King RA. A gene causing Hermansky–Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2. Am J Hum Genet 1995;57:755–65.PubMedGoogle Scholar
  3. 3.
    Fukai K, Oh J, Frenk E, Almodovar C, Spritz RA. Linkage disequilibrium mapping of the gene for Hermansky–Pudlak syndrome to chromosome 10q23.1-q23.3. Hum Mol Genet 1995;4:1665–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Hazelwood S, Shotelersuk V, Wildenberg SC, Chen D, Iwata F, Kaiser-Kupfer MI, White JG, King RA, Gahl WA. Evidence for locus heterogeneity in Puerto Ricans with Hermansky–Pudlak syndrome. Am J Hum Genet 1997;61:1088–94.CrossRefPubMedGoogle Scholar
  5. 5.
    Oh J, Bailin T, Fukai K, Feng GH, Ho L, Mao JI, Frenk E, Tamura N, Spritz RA. Positional cloning of a gene for Hermansky–Pudlak syndrome, a disorder of cytoplasmic organelles. Nat Genet 1996;14:300–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Oh J, Ho L, Ala-Mello S, Amato D, Armstrong L, Bellucci S, Carakushansky G, Ellis JP, Fong CT, Green JS, et al. Mutation analysis of patients with Hermansky–Pudlak syndrome: A frameshift hot spot in the HPS gene and apparent locus heterogeneity. Am J Hum Genet 1998;62:593–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT, Gahl WA, et al. Mutation of a new gene causes a unique form of Hermansky–Pudlak syndrome in a genetic isolate of central Puerto Rico. Nat Genet 2001;28:376–80.CrossRefPubMedGoogle Scholar
  8. 8.
    Santiago Borrero PJ, Rodriguez-Perez Y, Renta JY, Izquierdo NJ, Del Fierro L, Munoz D, Molina NL, Ramirez S, Pagan-Mercado G, Ortiz I, et al. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky–Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol 2006;126:85–90.CrossRefPubMedGoogle Scholar
  9. 9.
    Nakatani Y, Nakamura N, Sano J, Inayama Y, Kawano N, Yamanaka S, Miyagi Y, Nagashima Y, Ohbayashi C, Mizushima M, et al. Interstitial pneumonia in Hermansky–Pudlak syndrome: Significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes. Virchows Arch 2000;437:304–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Morgan NV, Pasha S, Johnson CA, Ainsworth JR, Eady RA, Dawood B, McKeown C, Trembath RC, Wilde J, Watson SP, et al. A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky–Pudlak syndrome (HPS8. Am J Hum Genet 2006;78:160–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Swank RT, Novak EK, McGarry MP, Rusiniak ME, Feng L. Mouse models of Hermansky Pudlak syndrome: A review. Pigment Cell Res 1998;11:60–80.CrossRefPubMedGoogle Scholar
  12. 12.
    Huizing M, Boissy RE, Gahl WA. Hermansky–Pudlak syndrome: Vesicle formation from yeast to man. Pigment Cell Res 2002;15:405–19.CrossRefPubMedGoogle Scholar
  13. 13.
    Li W, Rusiniak ME, Chintala S, Gautam R, Novak EK, Swank RT. Murine Hermansky–Pudlak syndrome genes: Regulators of lysosome-related organelles. Bioessays 2004;26:616–28.CrossRefPubMedGoogle Scholar
  14. 14.
    Dell’Angelica EC, Shotelersuk V, Aguilar RC, Gahl WA, Bonifacino JS. Altered trafficking of lysosomal proteins in Hermansky–Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor. Mol Cell 1999;3:11–21.CrossRefPubMedGoogle Scholar
  15. 15.
    Feng L, Rigatti BW, Novak EK, Gorin MB, Swank RT. Genomic structure of the mouse Ap3b1 gene in normal and pearl mice. Genomics 2000;69:370–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Feng L, Seymour AB, Jiang S, To A, Peden AA, Novak EK, Zhen L, Rusiniak ME, Eicher EM, Robinson MS, et al. The beta3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky–Pudlak syndrome and night blindness. Hum Mol Genet 1999;8:323–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Dell’Angelica EC. The building BLOC(k)s of lysosomes and related organelles. Curr Opin Cell Biol 2004;16:458–64.CrossRefPubMedGoogle Scholar
  18. 18.
    Gautam R, Chintala S, Li W, Zhang Q, Tan J, Novak EK, Di Pietro SM, Dell’Angelica EC, Swank RT. The Hermansky–Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). J Biol Chem 2004;279:12935–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Li W, Feng Y, Hao C, Guo X, Cui Y, He M, He X. The BLOC interactomes form a network in endosomal transport. J Genet Genomics 2007;34:669–82.CrossRefPubMedGoogle Scholar
  20. 20.
    Setty SR, Tenza D, Truschel ST, Chou E, Sviderskaya EV, Theos AC, Lamoreux ML, Di Pietro SM, Starcevic M, Bennett DC, et al. BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol Biol Cell 2007;18:768–80.CrossRefPubMedGoogle Scholar
  21. 21.
    Di Pietro SM, Falcon-Perez JM, Tenza D, Setty SR, Marks MS, Raposo G, Dell’Angelica EC. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol Biol Cell 2006;17:4027–38.CrossRefPubMedGoogle Scholar
  22. 22.
    Boissy RE, Nordlund JJ. Molecular basis of congenital hypopigmentary disorders in humans: A review. Pigment Cell Res 1997;10:12–24.CrossRefPubMedGoogle Scholar
  23. 23.
    Sarangarajan R, Budev A, Zhao Y, Gahl WA, Boissy RE. Abnormal translocation of tyrosinase and tyrosinase-related protein 1 in cutaneous melanocytes of Hermansky–Pudlak Syndrome and in melanoma cells transfected with anti-sense HPS1 cDNA. J Invest Dermatol 2001;117:641–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Richmond B, Huizing M, Knapp J, Koshoffer A, Zhao Y, Gahl WA, Boissy RE. Melanocytes derived from patients with Hermansky–Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking. J Invest Dermatol 2005;124:420–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Huizing M, Sarangarajan R, Strovel E, Zhao Y, Gahl WA, Boissy RE. AP-3 mediates tyrosinase but not TRP-1 trafficking in human melanocytes. Mol Biol Cell 2001;12:2075–85.PubMedGoogle Scholar
  26. 26.
    White JG. Membrane defects in inherited disorders of platelet function. Am J Pediatr Hematol Oncol 1982;4:83–94.PubMedGoogle Scholar
  27. 27.
    Weiss HJ, Lages B, Vicic W, Tsung LY, White JG. Heterogeneous abnormalities of platelet dense granule ultrastructure in 20 patients with congenital storage pool deficiency. Br J Haematol 1993;83:282–95.CrossRefPubMedGoogle Scholar
  28. 28.
    McKeown LP, Hansmann KE, Wilson O, Gahl W, Gralnick HR, Rosenfeld KE, Rosenfeld SJ, Horne MK, Rick ME. Platelet von Willebrand factor in Hermansky–Pudlak syndrome. Am J Hematol 1998;59:115–20.CrossRefPubMedGoogle Scholar
  29. 29.
    Huizing M, Parkes JM, Helip-Wooley A, White JG, Gahl WA. Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky–Pudlak syndrome. Platelets 2007;18:150–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Garay SM, Gardella JE, Fazzini EP, Goldring RM. Hermansky–Pudlak syndrome. Pulmonary manifestations of a ceroid storage disorder. Am J Med 1979;66:737–47.CrossRefPubMedGoogle Scholar
  31. 31.
    Ohbayashi C, Kanomata N, Imai Y, Ito H, Shimasaki H. Hermansky–Pudlak syndrome; a case report with analysis of auto-fluorescent ceroid-like pigments. Gerontology 1995;41 Suppl 2:297–303.CrossRefPubMedGoogle Scholar
  32. 32.
    Reynolds SP, Davies BH, Gibbs AR. Diffuse pulmonary fibrosis and the Hermansky–Pudlak syndrome: Clinical course and postmortem findings. Thorax 1994;49:617–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Thomas de Montpreville V, Mussot S, Dulmet E, Dartevelle P. [Pulmonary fibrosis in Hermansky–Pudlak syndrome is not fully usual]. Ann Pathol 2006;26:445–9.CrossRefPubMedGoogle Scholar
  34. 34.
    White DA, Smith GJ, Cooper JA Jr., Glickstein M, Rankin JA. Hermansky–Pudlak syndrome and interstitial lung disease: Report of a case with lavage findings. Am Rev Respir Dis 1984;130:138–41.PubMedGoogle Scholar
  35. 35.
    Pierson DM, Ionescu D, Qing G, Yonan AM, Parkinson K, Colby TC, Leslie K. Pulmonary fibrosis in Hermansky–Pudlak syndrome. a case report and review. Respiration 2006;73:382–95.CrossRefPubMedGoogle Scholar
  36. 36.
    Toro J, Turner M, Gahl WA. Dermatologic manifestations of Hermansky–Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene. Arch Dermatol 1999;135:774–80.CrossRefPubMedGoogle Scholar
  37. 37.
    Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky–Pudlak syndrome). N Engl J Med 1998;338:1258–64.CrossRefPubMedGoogle Scholar
  38. 38.
    Schallreuter KU, Frenk E, Wolfe LS, Witkop CJ, Wood JM. Hermansky–Pudlak syndrome in a Swiss population. Dermatology 1993;187:248–56.CrossRefPubMedGoogle Scholar
  39. 39.
    Hermos CR, Huizing M, Kaiser-Kupfer MI, Gahl WA. Hermansky–Pudlak syndrome type 1: Gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases. Hum Mutat 2002;20:482.CrossRefPubMedGoogle Scholar
  40. 40.
    Horikawa T, Araki K, Fukai K, Ueda M, Ueda T, Ito S, Ichihashi M. Heterozygous HPS1 mutations in a case of Hermansky–Pudlak syndrome with giant melanosomes. Br J Dermatol 2000;143:635–40.CrossRefPubMedGoogle Scholar
  41. 41.
    Ito S, Suzuki T, Inagaki K, Suzuki N, Takamori K, Yamada T, Nakazawa M, Hatano M, Takiwaki H, Kakuta Y, et al. High frequency of Hermansky–Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. J Invest Dermatol 2005;125:715–20.CrossRefPubMedGoogle Scholar
  42. 42.
    Zhen L, Jiang S, Feng L, Bright NA, Peden AA, Seymour AB, Novak EK, Elliott R, Gorin MB, Robinson MS, et al. Abnormal expression and subcellular distribution of subunit proteins of the AP-3 adaptor complex lead to platelet storage pool deficiency in the pearl mouse. Blood 1999;94:146–55.PubMedGoogle Scholar
  43. 43.
    Sugita M, Cao X, Watts GF, Rogers RA, Bonifacino JS, Brenner MB. Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells. Immunity 2002;16:697–706.CrossRefPubMedGoogle Scholar
  44. 44.
    Clark RH, Stinchcombe JC, Day A, Blott E, Booth S, Bossi G, Hamblin T, Davies EG, Griffiths GM. Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse. Nat Immunol 2003;4:1111–20.CrossRefPubMedGoogle Scholar
  45. 45.
    Benson KF, Li FQ, Person RE, Albani D, Duan Z, Wechsler J, Meade-White K, Williams K, Acland GM, Niemeyer G, et al. Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase. Nat Genet 2003;35:90–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Horwitz M, Benson KF, Duan Z, Li FQ, Person RE. Hereditary neutropenia: Dogs explain human neutrophil elastase mutations. Trends Mol Med 2004;10:163–70.CrossRefPubMedGoogle Scholar
  47. 47.
    Huizing M, Anikster Y, Fitzpatrick DL, Jeong AB, D’Souza M, Rausche M, Toro JR, Kaiser-Kupfer MI, White JG, Gahl WA. Hermansky–Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican patients with hypopigmentation and platelet storage-pool deficiency. Am J Hum Genet 2001;69:1022–32.CrossRefPubMedGoogle Scholar
  48. 48.
    Di Pietro SM, Falcon-Perez JM, Dell’Angelica EC. Characterization of BLOC-2, a complex containing the Hermansky–Pudlak syndrome proteins HPS3, HPS5 and HPS6. Traffic 2004;5:276–83.CrossRefPubMedGoogle Scholar
  49. 49.
    Boissy RE, Richmond B, Huizing M, Helip-Wooley A, Zhao Y, Koshoffer A, Gahl WA. Melanocyte-specific proteins are aberrantly trafficked in melanocytes of Hermansky–Pudlak syndrome-type 3. Am J Pathol 2005;166:231–40.PubMedGoogle Scholar
  50. 50.
    Suzuki T, Li W, Zhang Q, Karim A, Novak EK, Sviderskaya EV, Hill SP, Bennett DC, Levin AV, Nieuwenhuis HK, et al. Hermansky–Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Nat Genet 2002;30:321–4.PubMedGoogle Scholar
  51. 51.
    Anderson PD, Huizing M, Claassen DA, White J, Gahl WA. Hermansky–Pudlak syndrome type 4 (HPS-4): Clinical and molecular characteristics. Hum Genet 2003;113:10–7.PubMedGoogle Scholar
  52. 52.
    Huizing M, Hess R, Dorward H, Claassen DA, Helip-Wooley A, Kleta R, Kaiser-Kupfer MI, White JG, Gahl WA. Cellular, molecular and clinical characterization of patients with Hermansky–Pudlak syndrome type 5. Traffic 2004;5:711–22.CrossRefPubMedGoogle Scholar
  53. 53.
    Helip-Wooley A, Westbroek W, Dorward HM, Koshoffer A, Huizing M, Boissy RE, Gahl WA. Improper trafficking of melanocyte-specific proteins in Hermansky–Pudlak syndrome type-5. J Invest Dermatol 2007;127:1471–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Schreyer-Shafir N, Huizing M, Anikster Y, Nusinker Z, Bejarano-Achache I, Maftzir G, Resnik L, Helip-Wooley A, Westbroek W, Gradstein L, et al. A new genetic isolate with a unique phenotype of syndromic oculocutaneous albinism: Clinical, molecular, and cellular characteristics. Hum Mutat 2006;27:1158.CrossRefPubMedGoogle Scholar
  55. 55.
    Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O’Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, et al. Hermansky–Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1. Nat Genet 2003;35:84–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Gonzalez-Conejero R, Rivera J, Escolar G, Zuazu-Jausoro I, Vicente V, Corral J. Molecular, ultrastructural and functional characterization of a Spanish family with Hermansky–Pudlak syndrome: Role of insC974 in platelet function and clinical relevance. Br J Haematol 2003;123:132–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Izquierdo NJ, Townsend W, Hussels IE. Ocular findings in the Hermansky–Pudlak syndrome. Trans Am Ophthalmol Soc 1995;93:191–200; discussion 200–192.PubMedGoogle Scholar
  58. 58.
    Iwata F, Reed GF, Caruso RC, Kuehl EM, Gahl WA, Kaiser-Kupfer MI. Correlation of visual acuity and ocular pigmentation with the 16-bp duplication in the HPS-1 gene of Hermansky–Pudlak syndrome, a form of albinism. Ophthalmology 2000;107:783–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Gradstein L, FitzGibbon EJ, Tsilou ET, Rubin BI, Huizing M, Gahl WA. Eye movement abnormalities in Hermansky–Pudlak syndrome. J Aapos 2005;9:369–78.CrossRefPubMedGoogle Scholar
  60. 60.
    Witkop CJ, Nunez Babcock M, Rao GH, Gaudier F, Summers CG, Shanahan F, Harmon KR, Townsend D, Sedano HO, King RA, et al. Albinism and Hermansky–Pudlak syndrome in Puerto Rico. Bol Asoc Med P R 1990;82:333–9.PubMedGoogle Scholar
  61. 61.
    DePinho RA, Kaplan KL. The Hermansky–Pudlak syndrome. Report of three cases and review of pathophysiology and management considerations. Medicine (Baltimore) 1985;64:192–202.Google Scholar
  62. 62.
    Witkop CJ Jr., Bowie EJ, Krumwiede MD, Swanson JL, Plumhoff EA, White JG. Synergistic effect of storage pool deficient platelets and low plasma von Willebrand factor on the severity of the hemorrhagic diathesis in Hermansky–Pudlak syndrome. Am J Hematol 1993;44:256–9.CrossRefPubMedGoogle Scholar
  63. 63.
    Kouklakis G, Efremidou EI, Papageorgiou MS, Pavlidou E, Manolas KJ, Liratzopoulos N. Complicated Crohn’s-like colitis, associated with Hermansky–Pudlak syndrome, treated with Infliximab: A case report and brief review of the literature. J Med Case Reports 2007;1:176.CrossRefPubMedGoogle Scholar
  64. 64.
    Erzin Y, Cosgun S, Dobrucali A, Tasyurekli M, Erdamar S, Tuncer M. Complicated granulomatous colitis in a patient with Hermansky–Pudlak syndrome, successfully treated with infliximab. Acta Gastroenterol Belg 2006;69:213–6.PubMedGoogle Scholar
  65. 65.
    Grucela AL, Patel P, Goldstein E, Palmon R, Sachar DB, Steinhagen RM. Granulomatous enterocolitis associated with Hermansky–Pudlak syndrome. Am J Gastroenterol 2006;101:2090–5.CrossRefPubMedGoogle Scholar
  66. 66.
    Hazzan D, Seward S, Stock H, Zisman S, Gabriel K, Harpaz N, Bauer JJ. Crohn’s-like colitis, enterocolitis and perianal disease in Hermansky–Pudlak syndrome. Colorectal Dis 2006;8:539–43.CrossRefPubMedGoogle Scholar
  67. 67.
    Mahadeo R, Markowitz J, Fisher S, Daum F. Hermansky–Pudlak syndrome with granulomatous colitis in children. J Pediatr 1991;118:904–6.CrossRefPubMedGoogle Scholar
  68. 68.
    Sandberg-Gertzen H, Eid R, Jarnerot G. Hermansky–Pudlak syndrome with colitis and pulmonary fibrosis. Scand J Gastroenterol 1999;34:1055–6.CrossRefPubMedGoogle Scholar
  69. 69.
    Schinella RA, Greco MA, Cobert BL, Denmark LW, Cox RP. Hermansky–Pudlak syndrome with granulomatous colitis. Ann Intern Med 1980;92:20–3.PubMedGoogle Scholar
  70. 70.
    Hussain N, Quezado M, Huizing M, Geho D, White JG, Gahl W, Mannon P. Intestinal disease in Hermansky–Pudlak syndrome: Occurrence of colitis and relation to genotype. Clin Gastroenterol Hepatol 2006;4:73–80.CrossRefPubMedGoogle Scholar
  71. 71.
    Avila NA, Brantly M, Premkumar A, Huizing M, Dwyer A, Gahl WA. Hermansky–Pudlak syndrome: Radiography and CT of the chest compared with pulmonary function tests and genetic studies. AJR Am J Roentgenol 2002;179:887–92.PubMedGoogle Scholar
  72. 72.
    Brantly M, Avila NA, Shotelersuk V, Lucero C, Huizing M, Gahl WA. Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky–Pudlak syndrome, due to mutations in HPS-1. Chest 2000;117:129–36.CrossRefPubMedGoogle Scholar
  73. 73.
    Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B. Effect of pirfenidone on the pulmonary fibrosis of Hermansky–Pudlak syndrome. Mol Genet Metab 2002;76:234–42.CrossRefPubMedGoogle Scholar
  74. 74.
    Shulenin S, Nogee LM, Annilo T, Wert SE, Whitsett JA, Dean M. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med 2004;350:1296–303.CrossRefPubMedGoogle Scholar
  75. 75.
    Witkop CJ, Townsend D, Bitterman PB, Harmon K. The role of ceroid in lung and gastrointestinal disease in Hermansky–Pudlak syndrome. Adv Exp Med Biol 1989;266:283–96; discussion 297.PubMedGoogle Scholar
  76. 76.
    Rouhani FN, Brantly ML, Markello TC, Helip-Wooley A, O’Brien K, Hess R, Huizing M, Gahl WA, Gochuico BR. Alveolar macrophage dysregulation in Hermansky-Pudlak sydrome type 1. Am J Respir Crit Care Med 2009;180:1114–21.Google Scholar
  77. 77.
    Enders A, Zieger B, Schwarz K, Yoshimi A, Speckmann C, Knoepfle EM, Kontny U, Muller C, Nurden A, Rohr J, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky–Pudlak syndrome type II. Blood 2006;108:81–7.CrossRefPubMedGoogle Scholar
  78. 78.
    Fontana S, Parolini S, Vermi W, Booth S, Gallo F, Donini M, Benassi M, Gentili F, Ferrari D, Notarangelo LD, et al. Innate immunity defects in Hermansky–Pudlak type 2 syndrome. Blood 2006;107:4857–64.CrossRefPubMedGoogle Scholar
  79. 79.
    Huizing M, Scher CD, Strovel E, Fitzpatrick DL, Hartnell LM, Anikster Y, Gahl WA. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky–Pudlak syndrome type 2. Pediatr Res 2002;51:150–8.CrossRefPubMedGoogle Scholar
  80. 80.
    Shanahan F, Randolph L, King R, Oseas R, Brogan M, Witkop C, Rotter J, Targan S. Hermansky–Pudlak syndrome: An immunologic assessment of 15 cases. Am J Med 1988;85:823–8.CrossRefPubMedGoogle Scholar
  81. 81.
    Shotelersuk V, Dell’Angelica EC, Hartnell L, Bonifacino JS, Gahl WA. A new variant of Hermansky–Pudlak syndrome due to mutations in a gene responsible for vesicle formation. Am J Med 2000;108:423–7.CrossRefPubMedGoogle Scholar
  82. 82.
    Nazarian R, Huizing M, Helip-Wooley A, Starcevic M, Gahl WA, Dell’Angelica EC. An immunoblotting assay to facilitate the molecular diagnosis of Hermansky–Pudlak syndrome. Mol Genet Metab 2008;93:134–44.CrossRefPubMedGoogle Scholar
  83. 83.
    Cordova A, Barrios NJ, Ortiz I, Rivera E, Cadilla C, Santiago-Borrero PJ. Poor response to desmopressin acetate (DDAVP) in children with Hermansky–Pudlak syndrome. Pediatr Blood Cancer 2005;44:51–4.CrossRefPubMedGoogle Scholar
  84. 84.
    Lederer DJ, Kawut SM, Sonett JR, Vakiani E, Seward SL Jr., White JG, Wilt JS, Marboe CC, Gahl WA, Arcasoy SM. Successful bilateral lung transplantation for pulmonary fibrosis associated with the Hermansky–Pudlak syndrome. J Heart Lung Transplant 2005;24:1697–9.CrossRefPubMedGoogle Scholar
  85. 85.
    Garrison NA, Yi Z, Cohen-Barak O, Huizing M, Hartnell LM, Gahl WA, Brilliant MH. P gene mutations in patients with oculocutaneous albinism and findings suggestive of Hermansky–Pudlak syndrome. J Med Genet 2004;41:e86.CrossRefPubMedGoogle Scholar
  86. 86.
    Gardner JM, Wildenberg SC, Keiper NM, Novak EK, Rusiniak ME, Swank RT, Puri N, Finger JN, Hagiwara N, Lehman AL, et al. The mouse pale ear (ep) mutation is the homologue of human Hermansky–Pudlak syndrome. Proc Natl Acad Sci U S A 1997;94:9238–43.CrossRefPubMedGoogle Scholar
  87. 87.
    Novak EK, Sweet HO, Prochazka M, Parentis M, Soble R, Reddington M, Cairo A, Swank RT. Cocoa: A new mouse model for platelet storage pool deficiency. Br J Haematol 1988;69:371–8.CrossRefPubMedGoogle Scholar
  88. 88.
    Suzuki T, Li W, Zhang Q, Novak EK, Sviderskaya EV, Wilson A, Bennett DC, Roe BA, Swank RT, Spritz RA. The gene mutated in cocoa mice, carrying a defect of organelle biogenesis, is a homologue of the human Hermansky–Pudlak syndrome-3 gene. Genomics 2001;78:30–7.CrossRefPubMedGoogle Scholar
  89. 89.
    Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O’Brien EP, Zhang Y, et al. Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky–Pudlak syndrome types 5 and 6. Nat Genet 2003;33:145–53.CrossRefPubMedGoogle Scholar
  90. 90.
    Clark R, Griffiths GM. Lytic granules, secretory lysosomes and disease. Curr Opin Immunol 2003;15:516–21.CrossRefPubMedGoogle Scholar
  91. 91.
    Feng L, Novak EK, Hartnell LM, Bonifacino JS, Collinson LM, Swank RT. The Hermansky–Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes. Blood 2002;99:1651–8.CrossRefPubMedGoogle Scholar
  92. 92.
    Lyerla TA, Rusiniak ME, Borchers M, Jahreis G, Tan J, Ohtake P, Novak EK, Swank RT. Aberrant lung structure, composition, and function in a murine model of Hermansky–Pudlak syndrome. Am J Physiol Lung Cell Mol Physiol 2003;285:L643–L53.PubMedGoogle Scholar
  93. 93.
    Guttentag SH, Akhtar A, Tao JQ, Atochina E, Rusiniak ME, Swank RT, Bates SR. Defective surfactant secretion in a mouse model of Hermansky–Pudlak syndrome. Am J Respir Cell Mol Biol 2005;33:14–21.CrossRefPubMedGoogle Scholar
  94. 94.
    Gautam R, Novak EK, Tan J, Wakamatsu K, Ito S, Swank RT. Interaction of Hermansky–Pudlak Syndrome genes in the regulation of lysosome-related organelles. Traffic 2006;7:779–92.CrossRefPubMedGoogle Scholar
  95. 95.
    Young LR, Borchers MT, Allen HL, Gibbons RS, McCormack FX. Lung-restricted macrophage activation in the pearl mouse model of Hermansky–Pudlak syndrome. J Immunol 2006;176:4361–8.PubMedGoogle Scholar
  96. 96.
    Young LR, Pasula R, Gulleman PM, Deutsch GH, McCormack FX. Susceptibility of Hermansky–Pudlak mice to bleomycin-induced type II cell apoptosis and fibrosis. Am J Respir Cell Mol Biol 2007;37:67–74.CrossRefPubMedGoogle Scholar
  97. 97.
    Yoshioka Y, Kumasaka T, Ishidoh K, Kominami E, Mitani K, Hosokawa Y, Fukuchi Y. Inflammatory response and cathepsins in silica-exposed Hermansky–Pudlak syndrome model pale ear mice. Pathol Int 2004;54:322–31.CrossRefPubMedGoogle Scholar
  98. 98.
    Brooks BP, Larson DM, Chan CC, Kjellstrom S, Smith RS, Crawford MA, Lamoreux L, Huizing M, Hess R, Jiao X, et al. Analysis of ocular hypopigmentation in Rab38cht/cht mice. Invest Ophthalmol Vis Sci 2007;48:3905–13.CrossRefPubMedGoogle Scholar
  99. 99.
    Osanai K, Hatta R, Higuchi J, Miwa T, Toga H 2007. Rab38-deficient rats show phenotype of Hermansky–Pudlak syndrome. Proc Am Thoracic Soc. A341.Google Scholar
  100. 100.
    Bahadori R, Rinner O, Schonthaler HB, Biehlmaier O, Makhankov YV, Rao P, Jagadeeswaran P, Neuhauss SC. The Zebrafish fade out mutant: A novel genetic model for Hermansky–Pudlak syndrome. Invest Ophthalmol Vis Sci 2006;47:4523–31.CrossRefPubMedGoogle Scholar
  101. 101.
    Maldonado E, Hernandez F, Lozano C, Castro ME, Navarro RE. The zebrafish mutant vps18 as a model for vesicle-traffic related hypopigmentation diseases. Pigment Cell Res 2006;19:315–26.CrossRefPubMedGoogle Scholar
  102. 102.
    Schonthaler HB, Fleisch VC, Biehlmaier O, Makhankov Y, Rinner O, Bahadori R, Geisler R, Schwarz H, Neuhauss SC, Dahm R. The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles. Development 2008;135:387–99.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lisa R. Young
    • 1
  • William A. Gahl
    • 2
  1. 1.Department of Pediatrics and Department of Internal MedicineUniversity of Cincinnati School of Medicine and Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA

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