Hermansky-Pudlak Syndrome Clinical Presentation

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

History

Past ocular history in patients with Hermansky-Pudlak syndrome should include the following:

  • Photophobia
  • Previous eyeglasses, bifocals, eyeglasses tints, low vision aids
  • Amblyopia therapy
  • Eye deviations and strabismus surgery

Past systemic history in patients with Hermansky-Pudlak syndrome should include the following:

  • Bleeding diathesis: The most important questions when evaluating a patient with oculocutaneous albinism (OCA) are as follows: Do you bruise easily? Does your child bruise easily? Ask about aspirin and its derivatives intake.
  • The review of systems should include pulmonary symptoms associated to pulmonary fibrosis, a history of previous pulmonary function tests, and steroid therapy.
  • Evaluate symptoms associated with colitis, such as abdominal pain, diarrhea, lower gastrointestinal bleeding, and previous intestinal surgery.
  • Female patients with the syndrome should be asked about menometrorrhagia, abnormal uterine bleeding, and gynecologic surgery.
  • A history of sun exposure, sunblock application, skin biopsies, and malignancies should be obtained.

The family history of patients with Hermansky-Pudlak syndrome should include the following: nationality, parental consanguinity, and incidence of HPS in other family members.

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Physical

A wide ocular phenotypic variety exists in patients with Hermansky-Pudlak syndrome. Ocular findings in these patients include the following:[6, 7, 8]

  • Poor visual acuity: Best-corrected visual acuity in patients with Hermansky-Pudlak syndrome ranges from 20/60 to 20/400 in the Snellen chart.
  • Refractive errors that range from high myopia to hyperopia may be present. With the rule astigmatism is common.
  • Strabismus: Both horizontal and vertical have been reported.
  • Patients with Hermansky-Pudlak syndrome have congenital nystagmus. The most common types of strabismus found in patients with the syndrome are esotropia and exotropia. Vertical deviations have been reported.
  • Patients with Hermansky-Pudlak syndrome have various anterior segment abnormalities that include the following: a prominent Schwalbe line, iris transillumination, and presenile cataracts. Iris transillumination varies from almost total transillumination (pigment found at the collarette) to minimal peripheral transillumination (mostly in patients with HPS type 3).
  • Patients with Hermansky-Pudlak syndrome have foveal hypoplasia. Vascular architecture varies. Macular transparency (grading of choroidal vessels visibility) ranges from transparent to opaque. All patients have albinotic mid-periphery.
  • Previous studies report that patients with Hermansky-Pudlak syndrome have poor binocular vision.
  • Studies show that approximately 50% of patients with Hermansky-Pudlak syndrome have color vision defects upon HRR pseudoisochromatic plates testing.
  • Visual-evoked potentials show excessive decussation of optic nerve fibers.
  • Optical coherence tomography in patients with albinism shows that patients with OCA (all types included) have thicker foveas than the general population. This may be due to absence of a foveal pit as part of foveal hypoplasia in patients with OCA. Conversely, patients with OCA have lower macular volumes than the general population. This finding is compatible with loss of retinal nuclear layers in patients with OCA.

Patients with Hermansky-Pudlak syndrome have a wide variety of phenotypic skin findings.

  • Hair color varies from light blonde to dark brown. Hair and skin pigmentation is darker in patients with HPS type 3.
  • Skin freckles, lentigines, actinic keratosis, and premalignant and malignant skin lesions may also be present.

Patients with Hermansky-Pudlak syndrome have several systemic findings:[9, 10, 11, 12]

  • Enamel hypoplasia
  • Since patients with Hermansky-Pudlak syndrome have bleeding tendencies, inspect the extremities for ecchymosis.
  • Patients should have a pneumologic evaluation, since more than 50% of patients with Hermansky-Pudlak syndrome have pulmonary fibrosis. Auscultate patients for wheezing.
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Causes

HPS is a group of autosomal recessive disorders. Therefore, consanguinity and geographical isolation increases the risk of affected offspring. Pseudodominance has been reported in the northwestern quarter of Puerto Rico, because of patients with the syndrome who marry carriers of the HPS genes in geographically isolated regions.

  • Seven genes may lead to HPS in humans. Fukai and coworkers identified an HPS gene, located in chromosome region 10q23.1-23.3 by using a positional cloning approach.[13] Genetic analysis of Puerto Rican patients identified a 16-base pair duplication/frameshift within exon 15. This results in a frameshift at codon Pro 496. This gene is called the HPS-1 gene.
  • Puerto Rican patients with HPS type 3 have all been homozygous for a 3,904-bp deletion in the HPS-3 gene, as described by Anikster and coworkers.[14]
  • However, further studies have shown evidence for locus heterogeneity in Puerto Ricans with the syndrome. Bailin and coworkers suggest that mutations in the adaptor-related code complex (termed AP-3) subunits may lead to some forms of HPS.[15] The AP-3 complex facilitates transport of vesicles from the trans-Golgi network and endosomal compartments. AP-3 interacts with tyrosine signals on proteins of lysosomes and other intracellular organelles.
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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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