Hermansky-Pudlak Syndrome 

  • Author: Natalio J Izquierdo, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: May 5, 2010
 

Background

In 1959, Hermansky and Pudlak described two patients with oculocutaneous albinism (OCA) who had bleeding diathesis. Both patients had pulmonary disease. Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of autosomal recessive disorders characterized by tyrosinase-positive oculocutaneous albinism (Ty-pos OCA), bleeding tendency diathesis, and systemic complications associated to lysosomal dysfunction, such as pulmonary fibrosis and colitis. Several types of HPS are described. In Puerto Rico, both type 1 (HPS type 1) and type 3 (HPS type 3) have been described.[1, 2, 3, 4, 5]

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Pathophysiology

Patients with the syndrome have Ty-pos OCA. As the name implies, both the visual and skin systems are affected. However, patients with the syndrome have a wide variety of phenotypic appearance. Patients with HPS have legal blindness, nystagmus, strabismus, iris transillumination, foveal hypoplasia, and albinotic retinal mid-periphery. Skin biopsies reveal a normal number of melanocytes. Melanosomes are reduced in both melanocytes and keratinocytes.

Patients with HPS have a bleeding tendency associated to poor platelet aggregation. Platelets in patients with the syndrome have abnormal aggregation with collagen, thrombin, epinephrine, and adenosine diphosphate (ADP). Electron microscopy (EM) shows that platelets in patients with the syndrome have a smaller quantity of dense bodies (DB). DB are needed for the second phase of platelet aggregation. They are storage sites for serotonin, calcium, and pyrophosphate. DB are visualized in unfixed, unstained, whole mount EM preparations due to their calcium content or by staining platelets with lead citrate and uranyl acetate.

Systemic complications are associated to accumulation of a ceroidlike substance in lysosomes of a variety of tissues. Ceroid deposition in patients with HPS may lead to pulmonary fibrosis, granulomatous enteropathic disease, and renal failure. This lysosomal defect has been reported in reticuloendothelial cells, bone marrow, and lung macrophages.

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Epidemiology

Frequency

United States

The various types of HPS are rare genetic diseases worldwide.

In Puerto Rico, 5 out of 6 patients with OCA have HPS. For this reason, in Puerto Rico, a patient with OCA has HPS until proven otherwise. If a patient in the continental United States has OCA and Puerto Rican family members, HPS must be ruled out.

HPS type 1 is the most common single gene disorder in Puerto Rico, being most prevalent in the northwestern quadrant of the island. Epidemiologic studies report that in this region, 1 out of 1,800 persons has the syndrome. In this area, approximately 1 out of 21 persons carries the gene encoding for HPS type 1. On the other hand, HPS type 3 is more prevalent in the central mountainous region of the Caribbean island.

International

Patients with HPS have been reported in other nations, including Holland, the United Kingdom, and Mexico. Further, it has been reported among Jews.

Mortality/Morbidity

Clinical studies show that over 70% of patients with HPS die of causes directly related to the syndrome. Systemic complications of the syndrome lead to an average patient survival age of 30-50 years. Death usually results from complications, such as pulmonary fibrosis in more than 50% of patients with the syndrome; hemorrhagic episodes in over 15% of patients with the syndrome; and granulomatous colitis in 15% of patients with the syndrome.

  • Most patients with the syndrome are legally blind. Best-corrected visual acuity in patients with the syndrome ranges from 20/60 to 20/400.
  • Patients with HPS have skin diseases. Clinical studies report that 80% of patients with HPS have freckles or lentigines. Solar keratoses, squamous cell, and basal cell carcinoma have been reported.

Sex

No sexual predilection exists, as the syndrome has an autosomal recessive inheritance pattern.

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Contributor Information and Disclosures
Author

Natalio J Izquierdo, MD  Former Associate Professor of Ophthalmology, University of Puerto Rico

Natalio J Izquierdo, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Society for Genetic Eye Diseases and Retinoblastoma, Pan-American Association of Ophthalmology, and Sociedad Puertorriquena de Oftalmologia

Disclosure: Nothing to disclose.

Coauthor(s)

William Townsend, MD  Retired Professor, Chairman, and Director, Department of Ophthalmology, University of Puerto Rico, Medical Sciences

William Townsend, MD is a member of the following medical societies: American Academy of Ophthalmology and American Ophthalmological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Andrew W Lawton, MD  Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD  Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Brian R Younge, MD  Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

References

  1. Walker M, Payne J, Wagner B, Vora A. Hermansky-Pudlak syndrome. Br J Haematol. Sep 2007;138(6):671. [Medline].

  2. Vincent LM, Adams D, Hess RA, Ziegler SG, Tsilou E, Golas G, et al. Hermansky-Pudlak syndrome type 1 in patients of Indian descent. Mol Genet Metab. Jul 2009;97(3):227-33. [Medline]. [Full Text].

  3. Spencer J, Rosengren S. Hermansky-Pudlak Syndrome in Pregnancy. Am J Perinatol. Apr 15 2009;[Medline].

  4. Hurford MT, Sebastiano C. Hermansky-pudlak syndrome: report of a case and review of the literature. Int J Clin Exp Pathol. Jan 1 2008;1(6):550-4. [Medline].

  5. Suzuki T, Tomita Y. Recent advances in genetic analyses of oculocutaneous albinism types 2 and 4. J Dermatol Sci. Jul 2008;51(1):1-9. [Medline].

  6. Gradstein L, FitzGibbon EJ, Tsilou ET, Rubin BI, Huizing M, Gahl WA. Eye movement abnormalities in hermansky-pudlak syndrome. J AAPOS. Aug 2005;9(4):369-78. [Medline].

  7. Tang J, Tsilou E, Caruso RC, Rubin B, Gahl WA. Bilateral staphylomas in a patient with Hermansky-Pudlak syndrome. Retina. Jan 2005;25(1):99-100. [Medline].

  8. Chong GT, Farsiu S, Freedman SF, Sarin N, Koreishi AF, Izatt JA. Abnormal foveal morphology in ocular albinism imaged with spectral-domain optical coherence tomography. Arch Ophthalmol. Jan 2009;127(1):37-44. [Medline].

  9. Echenique I, Garcia Gonzralez JM, Echenique IA, Izquierdo NJ, Mella JR, Barasorda E, et al. Hermansky Pudlak syndrome: an unusual form of procto-colitis. Bol Asoc Med P R. Jan-Mar 2008;100(1):76-9. [Medline].

  10. Lee AC, Poon KH, Lo WH, Wong LG. Chronic ulcerative gastroduodenitis as a first gastrointestinal manifestation of Hermansky-Pudlak syndrome in a 10-year-old child. World J Gastroenterol. May 14 2008;14(18):2939-41. [Medline].

  11. 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. Dec 8 2007;1:176. [Medline]. [Full Text].

  12. Lee AC, Poon KH, Lo WH, Wong LG. Chronic ulcerative gastroduodenitis as a first gastrointestinal manifestation of Hermansky-Pudlak syndrome in a 10-year-old child. World J Gastroenterol. May 14 2008;14(18):2939-41. [Medline].

  13. 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. Sep 1995;4(9):1665-9. [Medline].

  14. Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, 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. Aug 2001;28(4):376-80. [Medline].

  15. Bailin T, Oh J, Feng GH, Fukai K, Spritz RA. Organization and nucleotide sequence of the human Hermansky-Pudlak syndrome (HPS) gene. J Invest Dermatol. Jun 1997;108(6):923-7. [Medline].

  16. Witkop CJ, Nunez Babcock M, Rao GH, Gaudier F, Summers CG, Shanahan F, et al. Albinism and Hermansky-Pudlak syndrome in Puerto Rico. Bol Asoc Med P R. Aug 1990;82(8):333-9. [Medline].

  17. 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. Jan 2000;117(1):129-36. [Medline].

  18. DellAngelica 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. Jan 1999;3(1):11-21. [Medline].

  19. Hazelwood S, Shotelersuk V, Wildenberg SC, Chen D, Iwata F, Kaiser-Kupfer MI, et al. Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome. Am J Hum Genet. Nov 1997;61(5):1088-94. [Medline].

  20. 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. Apr 2000;107(4):783-9. [Medline].

  21. Izquierdo NJ, Townsend W, Hussels IE. Ocular findings in the Hermansky-Pudlak syndrome. Trans Am Ophthalmol Soc. 1995;93:191-200; discussion 200-2. [Medline].

  22. Oh J, Bailin T, Fukai K. Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles. Nat Genet. Nov 1996;14(3):300-6. [Medline].

  23. Reynolds SP, Davies BH, Gibbs AR. Diffuse pulmonary fibrosis and the Hermansky-Pudlak syndrome: clinical course and postmortem findings. Thorax. Jun 1994;49(6):617-8. [Medline].

  24. Schachne JP, Glaser N, Lee SH, Kress Y, Fisher M. Hermansky-Pudlak syndrome: case report and clinicopathologic review. J Am Acad Dermatol. May 1990;22(5 Pt 2):926-32. [Medline].

  25. Schinella RA, Greco MA, Cobert BL, Denmark LW, Cox RP. Hermansky-Pudlak syndrome with granulomatous colitis. Ann Intern Med. Jan 1980;92(1):20-3. [Medline].

  26. Simon JW, Adams RJ, Calhoun JH, Shapiro SS, Ingerman CM. Ophthalmic manifestations of the Hermansky-Pudlak syndrome (oculocutaneous albinism and hemorrhagic diathesis). Am J Ophthalmol. Jan 1982;93(1):71-7. [Medline].

  27. Summers CG, Knobloch WH, Witkop CJ Jr, King RA. Hermansky-Pudlak syndrome. Ophthalmic findings. Ophthalmology. Apr 1988;95(4):545-54. [Medline].

  28. 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. Jul 1999;135(7):774-80. [Medline].

  29. Van Dorp DB, Wijermans PW, Meire F, Vrensen G. The Hermansky-Pudlak syndrome. Variable reaction to 1-desamino-8D-arginine vasopressin for correction of the bleeding time. Ophthalmic Paediatr Genet. Sep 1990;11(3):237-44. [Medline].

 
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