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Dermatologic Manifestations of Hermansky-Pudlak Syndrome Clinical Presentation

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
Updated: Feb 05, 2016


Because patients with Hermansky-Pudlak syndrome have platelet dysfunction, albinism, and ceroid accumulation, clinical history that relates to these complications must be investigated.

When the intestines are infiltrated with ceroid, patients can have diarrhea, weight loss, cramps, and possibly blood in the stool. These manifestations resemble those of inflammatory bowel disease, with the onset of symptoms occurring in patients aged 12-30 years. Most of the patients with Hermansky-Pudlak syndrome–related bowel disease are Puerto Rican. Response to medical therapy is said to be poor. One article reported 2 children, aged 7 years and 3 years, with granulomatous colitis in association with Hermansky-Pudlak syndrome.[19] One of these children was Puerto Rican. Hazzan et al[20] noted Crohn disease–like colitis, enterocolitis, and perianal disease in a patient with Hermansky-Pudlak syndrome, suggesting that the intestinal pathology of Hermansky-Pudlak syndrome results from the development of classic Crohn disease.

Ceroid can infiltrate the pulmonary system as well. When the lungs are impaired in this fashion, shortness of breath and abnormal fatigue with exertion can occur. The disease can progress to pulmonary fibrosis, with scar tissue restricting the inflation of the lungs. Patients should be asked about previous pulmonary function tests and steroid therapy. Thomas de Montpréville et al[21] noted pulmonary fibrosis in a patient with Hermansky-Pudlak syndrome related to a defect in surfactant. This patient had undergone lung transplantation.

Hermansky-Pudlak syndrome impairs vision; thus, patients should be asked about photophobia, previous eyeglasses, bifocals, eyeglass tints, low-vision aids, amblyopia therapy, and strabismus surgery.

Patients with Hermansky-Pudlak syndrome are prone to skin cancers; thus, they should be asked about any new skin growths. A history of sun exposure, sunblock application, skin biopsy, and cancers should be obtained from patients.

Bleeding diathesis must be investigated. Persons with Hermansky-Pudlak syndrome may have a tendency to bruise easily or to experience frequent nosebleeds or prolonged bleeding. Epistaxis is the most frequent hemorrhagic manifestation. Patients with Hermansky-Pudlak syndrome can have unusual bleeding episodes (eg, heavy menstrual bleeding, bleeding with dental procedures). Patients should be asked about medications that affect bleeding and, thus, should be queried about the use of aspirin and aspirin derivatives. Persons should be asked if their children or parents bleed easily.

Women with Hermansky-Pudlak syndrome should be queried about pregnancies and pregnancy complications, menometrorrhagia, abnormal uterine bleeding, and gynecologic surgery. Therapy-refractory menorrhagia has been noted as the first manifestation of Hermansky-Pudlak syndrome.[22]

Family history is important in understanding Hermansky-Pudlak syndrome. Patients should be asked where their families originated. Puerto Rican ancestry is important and must be investigated. Parental consanguinity and family incidence of Hermansky-Pudlak syndrome need to be reviewed with patients.

In 2003, Iannello et al[23] described a new familial Hermansky-Pudlak syndrome clinical variant in 2 sisters, one aged 6 years and the other aged 23 years. They expressed the common symptoms of Hermansky-Pudlak syndrome, but they also had diffuse interstitial pulmonary disease as well as augmented platelet aggregation. They were very susceptible to bacterial infections.

Interestingly, Iannello et al[23] observed a urinary tract abnormality in a younger sister with Hermansky-Pudlak syndrome and a porencephalic cyst in an older sister with Hermansky-Pudlak syndrome. These developmental defects have been reported in persons with Cross syndrome (oculocerebral hypopigmentation syndrome), which is a syndrome that has evaded precise definition. These sisters seemed to have an overlapping of the phenotypic manifestations of different rare syndromes. The presence of ceroidlike autofluorescent material in urinary sediment, combined with the histologic aspects and the autofluorescence of oral mucosa biopsy specimens, was consistent with a ceroidlike lipofuscin storage problem.

Enders et al[24] noted lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II.

Interestingly, Hermansky-Pudlak syndrome is a bleeding defect, in part, but late-onset menstrual bleeding has been noted.[25]

In Hermansky-Pudlak syndrome type IV, which involves (BLOC)-3, impacts healthy subjects' working memory and impacts function deficits in those with schizophrenia; this is not surprising because HPS is a neural disease in part.[26]



Physical findings relate to albinism, which affects the skin and the eyes. Pulmonary fibrosis can also be evaluated on physical examination.

Skin findings in Hermansky-Pudlak syndrome are as follows:

  • Patients with Hermansky-Pudlak syndrome commonly have blond hair and pale skin, as demonstrated in the image below. Some have brown hair and brown eyes.
    The face of a Puerto Rican girl with Hermansky-Pud The face of a Puerto Rican girl with Hermansky-Pudlak syndrome. Note the blond hair and the pale skin.
  • Melanocytic nevi with dysplastic features, acanthosis nigricans–like lesions in the axillae and the neck, and trichomegaly have been reported to occur.
  • Metastatic skin involvement of granulomatous colitis in Hermansky-Pudlak syndrome has been reported. [27]

Ocular findings in Hermansky-Pudlak syndrome are as follows:

  • Ocular findings in patients with Hermansky-Pudlak syndrome include the following: poor visual acuity, refractive errors associated with with-the-rule astigmatism, strabismus, congenital nystagmus, prominent Schwalbe line, iris transillumination, foveal hypoplasia, and albinotic retinal mid periphery, as shown in the image below.
    Photo showing light brown eyes and a red reflectio Photo showing light brown eyes and a red reflection in the eyes.
  • Best-corrected visual acuity in patients with Hermansky-Pudlak syndrome ranges from 20/60 to 20/400 in the Snellen chart. Refractive errors range from high myopia to hyperopia.
  • Patients with Hermansky-Pudlak syndrome have congenital nystagmus. The most common types of strabismus found in patients with this 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.
  • Patients with Hermansky-Pudlak syndrome have pale optic nerves.
  • Patients with Hermansky-Pudlak syndrome have foveal hypoplasia. Vascular architecture varies. Macular transparency (grading visibility of choroidal vessels) ranges from transparent to opaque. Patients with Hermansky-Pudlak syndrome have albinotic mid periphery.
  • Patients with Hermansky-Pudlak syndrome can have poor binocular vision.
  • Patients with this syndrome have no color vision defects on Ishihara testing.
  • Visual-evoked potentials show excessive decussation of the optic nerve fibers.
  • Iris heterochromia with Hermansky-Pudlak syndrome has been reported. [28]

Pulmonary and cardiac findings in Hermansky-Pudlak syndrome are as follows:

  • Because patients can manifest with impaired lung function, auscultation of patients' lungs is important.
  • The lung's susceptibility to pulmonary fibrosis in Hermansky-Pudlak syndrome is determined by the alveolar epithelium. [29]
  • Because accumulation of ceroid in the heart can cause cardiomyopathy, auscultation of the heart is important.
  • A case of pulmonary alveolar proteinosis has been reported. [30]


Hermansky-Pudlak syndrome is an autosomal recessive disorder. Founder effects (one or several people who originated a population) are believed to cause the clustering of the disease in such places as Puerto Rico. The origin of Hermansky-Pudlak syndrome in Puerto Rico has been traced to a region of southern Spain, and a connection to cases in Holland is possible.

Other researchers have identified a second example of a founder mutation causing Hermansky-Pudlak syndrome in central Puerto Rico. They estimated that the large deletion in the HPS3 gene arose from 1880-1890. At that time, the ancestors of 3 of the 6 families with HPS-3 emigrated from the town of Ciales to the towns of Aibonito, Barranquitas, and Naranjito. Each of the 3 families could also trace their ancestry to 1 individual, Calixto Rivera, who brought his relatives to Aibonito and the surrounding area to deforest his land for tobacco growing.

Consanguinity and geographical isolation contribute to the continued occurrence of the disease.

Pseudodominance has been reported in the northwestern quarter of Puerto Rico and is associated with patients with Hermansky-Pudlak syndrome who marry persons who are carriers.

Contributor Information and Disclosures

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.


Ann M Johnson, MD Assistant Professor of Clinical Radiology, University of Pennsylvania School of Medicine; Director, Body MRI, Department of Radiology, Children’s Hospital of Philadelphia

Ann M Johnson, MD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America, Society for Pediatric Radiology, International Society for Magnetic Resonance in Medicine, Society of Computed Body Tomography and Magnetic Resonance

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


Smeena Khan, MD Private Practice, Adult and Pediatric Dermatology Associates

Smeena Khan, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

  1. Ammann S, Schulz A, Krägeloh-Mann I, Dieckmann NM, Niethammer K, Fuchs S, et al. Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome. Blood. 2016 Jan 7. [Medline].

  2. Badolato R, Parolini S. Novel insights from adaptor protein 3 complex deficiency. J Allergy Clin Immunol. 2007 Oct. 120(4):735-41; quiz 742-3. [Medline].

  3. Kurnik K, Bartsch I, Maul-Pavicic A, Ehl S, Sandrock-Lang K, Bidlingmaier C, et al. Novel mutation in Hermansky-Pudlak syndrome type 2 with mild immunological phenotype. Platelets. 2012 Dec 5. [Medline].

  4. Anikster Y, Huizing M, White J, 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 Aug. 28(4):376-80. [Medline].

  5. Helip-Wooley A, Westbroek W, Dorward HM, et al. Improper trafficking of melanocyte-specific proteins in Hermansky-Pudlak syndrome type-5. J Invest Dermatol. 2007 Jun. 127(6):1471-8. [Medline].

  6. Syrzycka M, McEachern LA, Kinneard J, et al. The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene. Genome. 2007 Jun. 50(6):548-56. [Medline].

  7. Li W, Zhang Q, Oiso N, 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 Sep. 35(1):84-9. [Medline]. [Full Text].

  8. Falcon-Perez JM, Romero-Calderon R, Brooks ES, Krantz DE, Dell'Angelica EC. The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5). Traffic. 2007 Feb. 8(2):154-68. [Medline].

  9. Nguyen T, Wei ML. Hermansky-Pudlak HPS1/pale ear gene regulates epidermal and dermal melanocyte development. J Invest Dermatol. 2007 Feb. 127(2):421-8. [Medline].

  10. Morgan NV, Pasha S, Johnson CA, et al. A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky-Pudlak syndrome (HPS8). Am J Hum Genet. 2006 Jan. 78(1):160-6. [Medline].

  11. Di Pietro SM, Falcon-Perez JM, Tenza D, et al. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol Biol Cell. 2006 Sep. 17(9):4027-38. [Medline].

  12. Sanchez-Guiu I, Torregrosa JM, Velasco F, Anton AI, Lozano ML, Vicente V, et al. Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case report of a new HPS-1 variant. Hamostaseologie. 2014. 34(4):301-9. [Medline].

  13. Jung J, Bohn G, Allroth A, et al. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. Blood. 2006 Jul 1. 108(1):362-9. [Medline].

  14. Salazar G, Zlatic S, Craige B, Peden AA, Pohl J, Faundez V. Hermansky-Pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal cells. J Biol Chem. 2009 Jan 16. 284(3):1790-802. [Medline]. [Full Text].

  15. Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, et al. Chitinase 3-like-1 and its receptors in Hermansky-Pudlak syndrome-associated lung disease. J Clin Invest. 2015 Aug 3. 125 (8):3178-92. [Medline].

  16. Torres-Serrant M, Ramirez SI, Cadilla CL, Ramos-Valencia G, Santiago-Borrero PJ. Newborn screening for hermansky-pudlak syndrome type 3 in puerto rico. J Pediatr Hematol Oncol. 2010 Aug. 32(6):448-53. [Medline].

  17. Merideth MA, Vincent LM, Sparks SE, et al. Hermansky-Pudlak syndrome in two African-American brothers. Am J Med Genet A. 2009 May. 149A(5):987-92. [Medline]. [Full Text].

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

  19. Grucela AL, Patel P, Goldstein E, Palmon R, Sachar DB, Steinhagen RM. Granulomatous enterocolitis associated with Hermansky-Pudlak syndrome. Am J Gastroenterol. 2006 Sep. 101(9):2090-5. [Medline].

  20. Hazzan D, Seward S, Stock H, et al. Crohn's-like colitis, enterocolitis and perianal disease in Hermansky-Pudlak syndrome. Colorectal Dis. 2006 Sep. 8(7):539-43. [Medline].

  21. Thomas de Montpreville V, Mussot S, Dulmet E, Dartevelle P. [Pulmonary fibrosis in Hermansky-Pudlak syndrome is not fully usual]. Ann Pathol. 2006 Dec. 26(6):445-9. [Medline].

  22. Lohse J, Gehrisch S, Tauer JT, Knofler R. Therapy refractory menorrhagia as first manifestation of Hermansky-Pudlak syndrome. Hamostaseologie. Nov 2011. 31:Suppl 1:S61-3. [Medline].

  23. Iannello S, Fabbri G, Bosco P, et al. A clinical variant of familial Hermansky-Pudlak syndrome. MedGenMed. 2003 Jan 27. 5(1):3. [Medline].

  24. Enders A, Zieger B, Schwarz K, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. 2006 Jul 1. 108(1):81-7. [Medline].

  25. Ray A, Ray S, Matthew JJ. Case Report : Hermansky Pudlak Syndrome (Presenting as late onset heavy Menstrual Bleeding). J Clin Diagn Res. 2013 Sep. 7(9):2023-4. [Medline].

  26. Kuratomi G, Saito A, Ozeki Y, Watanabe T, Fujii K, Shimoda K, et al. Association of the Hermansky-Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects. BMC Psychiatry. 2013 Oct. 30:13:276. [Medline].

  27. Weitz N, Patel V, Tlougan B, Mencin A, Kadenhe-Chiweshe A, Morel KD, et al. Metastatic Cutaneous Involvement of Granulomatous Colitis in Hermansky-Pudlak Syndrome. Pediatr Dermatol. 2012 Apr 4. [Medline].

  28. Radke P, Schimmenti LA, Schoonveld C, Bothun ED, Summers CG. The unique association of iris heterochromia with Hermansky-Pudlak syndrome. J AAPOS. 2013 Oct. 17(5):542-4. [Medline].

  29. Young LR, Gulleman PM, Bridges JP, Weaver TE, Deutsch GH, Blackwell TS, et al. The alveolar epithelium determines susceptibility to lung fibrosis in Hermansky-Pudlak syndrome. Am J Respir Crit Care Med. 2012 Nov. 186:1014-24. [Medline].

  30. Ozyilmaz E, Gunasti S, Kuyuku Y, Kuleci S, Hanta I, Kocabas A. Hermansky Pudlak Syndrome and Pulmonary Alveolar Proteinosis at the same patient: first case report in the world literature. Sarcoidosis Vasc Diffuse Lung Dis. 2013 Nov. 30(3):217-20. [Medline].

  31. 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 Oct. 179(4):887-92. [Medline].

  32. 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 Jan. 117(1):129-36. [Medline].

  33. Izquierdo NJ, Emanuelli A, Izquierdo JC, Garcia M, Cadilla C, Berrocal MH. Foveal thickness and macular volume in patients with oculocutaneous albinism. Retina. 2007 Nov-Dec. 27(9):1227-30. [Medline].

  34. 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 Apr-Jun. 69(2):213-6. [Medline].

  35. Beesley RD, Robinson RD, Stewart TL. Two successful vaginal births after cesarean section in a patient with Hermansky-Pudlak syndrome who was treated with 1-deamino-8-arginine-vasopression during labor. Mil Med. 2008 Oct. 173(10):1048-9. [Medline].

  36. 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 Jan. 44(1):51-4. [Medline].

  37. Felipez L, Gokhale R, Guandalini S. Hermansky-Pudlak Syndrome: Severe Colitis and Good Response to Infliximab. J Pediatr Gastroenterol Nutr. 2010 Jun 9. [Medline].

  38. O'Brien K, Troendle J, Gochuico BR, et al. Pirfenidone for the treatment of Hermansky-Pudlak syndrome pulmonary fibrosis. Mol Genet Metab. 2011 Jun. 103(2):128-34. [Medline].

  39. Feliciano NZ, Rivera E, Agrait E, Rodriguez K. Hermansky-Pudlak syndrome: dental management considerations. J Dent Child (Chic). 2006 Jan-Apr. 73(1):51-6. [Medline].

  40. Kanazu M, Arai T, Sugimoto C, Kitaichi M, Akira M, Abe Y, et al. An intractable case of Hermansky-Pudlak syndrome. Intern Med. 2014;. 53(22):2629-34. [Medline].

  41. Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2. 2:43. [Medline].

Photo showing light brown eyes and a red reflection in the eyes.
The face of a Puerto Rican girl with Hermansky-Pudlak syndrome. Note the blond hair and the pale skin.
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