Laboratory Studies

Genetic testing for the HPS1 gene, which most commonly occurs in Puerto Ricans, exists. A company called GeneDx can perform DNA screening for the 16–base pair duplication found in this variation of Hermansky-Pudlak syndrome (HPS).

Examination of blood platelets under an electron microscope can be performed. The absence of dense granules in the platelets is characteristic of this syndrome. The ultrastructure of ceroid-lipofuscin inclusions in macrophages in bone marrow, gut, and other tissues can be helpful, but the absence of dense granules in the platelets in association with albinism is diagnostic for Hermansky-Pudlak syndrome.

Standard blood tests (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT], platelet count, bleeding time) do not identify the platelet defect in Hermansky-Pudlak syndrome. Bleeding time of patients with Hermansky-Pudlak syndrome varies from 6-20 minutes. As many as 25% of patients with Hermansky-Pudlak syndrome have bleeding times within the normal reference range. Many patients with Hermansky-Pudlak syndrome have reduced von Willebrand factor activity in their platelets. There are some reports that these patients lack the CD63 marker on platelets.

Hair bulb incubation test can be used to classify patients with albinism into tyrosinase negative or tyrosinase positive. All patients with Hermansky-Pudlak syndrome have tyrosine-positive albinism. Clinical correlation is necessary because some patients with Hermansky-Pudlak syndrome may have false-negative results.

Imaging Studies

High-resolution CT is more sensitive than chest radiography in evaluating the extent of pulmonary disease in patients with Hermansky-Pudlak syndrome.^[37]Mild findings on high-resolution CT scans are paralleled by normal findings on chest radiographs. Common chest radiographic findings include reticulonodular interstitial pattern, perihilar fibrosis, and pleural thickening. High-resolution CT scans can show septal thickening, ground-glass opacities, and peribronchovascular thickening. One study noted that 82% of patients with Hermansky-Pudlak syndrome had abnormalities on high-resolution CT scans.^[38]

Owing to the increase risk of bleeding complications, patients with Hermansky-Pudlak syndrome who experience physical trauma should undergo CT scanning to rule out intra-articular, intracranial, and/or internal bleeding.

Other Tests

Vision should be tested and evaluated in a comprehensive fashion. Inspecting the iris for transillumination and the retina for findings compatible with albinism is useful, as is visual-acuity testing. In children with Hermansky-Pudlak syndrome, it is important to consider that impaired vision may affect their ability to learn. Therefore, educational and intellectual testing should be performed.

Patients with Hermansky-Pudlak syndrome should be evaluated by using pulmonary function tests. Forced vital capacity (FVC), forced expiratory volume (FEV), mean total lung capacity, mean vital capacity, and mean diffusing capacity of the lung for carbon monoxide decrease as interstitial lung disease progresses.

Some studies have reported that patients with albinism have a decreased bone density when compared with age-corrected control subjects, but the role of testing for bone density is unclear in Hermansky-Pudlak syndrome.

Procedures

Skin biopsy should be performed immediately on new skin lesions to evaluate for skin cancer.

Histologic Findings

Histologic and ultrastructural findings of non–sun-exposed skin showed melanocytes, with short dendritic processes and decreased numbers of melanosomes. Ultrastructural examination of platelets revealed greatly reduced numbers of delta granules. In adults, solar elastosis is usually present on sun-exposed skin.

Izquierdo et al^[39]found that patients with HPS-1 have thicker foveae than normal controls, perhaps because of the absence of a foveal pit as part of the foveal hypoplasia associated with Hermansky-Pudlak syndrome. Conversely, persons with Hermansky-Pudlak syndrome have lower macular volumes compared with the general population, perhaps because of a loss of retinal nuclear layers in these patients.

Treatment & Management

El-Chemaly S, Young LR. Hermansky-Pudlak Syndrome. Clin Chest Med. 2016 Sep. 37 (3):505-11. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Stearman RS, Cornelius AR, Young LR, Conklin DS, Mickler EA, Lu X, et al. Familial Pulmonary Fibrosis and Hermansky-Pudlak Syndrome Rare Missense Mutations in Context. Am J Respir Crit Care Med. 2019 Jul 15. 200 (2):253-256. [QxMD MEDLINE Link].
Dell'Acqua F, Saettini F, Castelli I, Badolato R, Notarangelo LD, Rizzari C. Hermansky-Pudlak syndrome type II and lethal hemophagocytic lymphohistiocytosis: Case description and review of the literature. J Allergy Clin Immunol Pract. 2019 Apr 8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2. 2:43. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Vicary GW, Vergne Y, Santiago-Cornier A, Young LR, Roman J. Pulmonary Fibrosis in Hermansky-Pudlak Syndrome. Ann Am Thorac Soc. 2016 Oct. 13 (10):1839-1846. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Iannello S, Fabbri G, Bosco P, et al. A clinical variant of familial Hermansky-Pudlak syndrome. MedGenMed. 2003 Jan 27. 5(1):3. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Jardón J, Izquierdo NJ, Renta JY, García-Rodríguez O, Cadilla CL. Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3). Ophthalmic Genet. 2016. 37 (1):89-94. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Felipez L, Gokhale R, Guandalini S. Hermansky-Pudlak Syndrome: Severe Colitis and Good Response to Infliximab. J Pediatr Gastroenterol Nutr. 2010 Jun 9. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

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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Author

Jaclyn Scholtz, MD Resident Physician, Department of Dermatology, Wright State University, Boonshoft School of Medicine

Jaclyn Scholtz, MD is a member of the following medical societies: American Academy of Dermatology, Ohio Dermatological Association, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Julian J Trevino, MD Professor and Chair of Dermatology, Dermatology Residency Program Director, Wright State University, Boonshoft School of Medicine; Chief, Division of Pediatric Dermatology, Dayton Children’s Hospital

Julian J Trevino, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Ohio Dermatological Association, Ohio State Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former 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: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

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.

Additional Contributors

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: Nothing to disclose.

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 for Advanced Body Imaging

Disclosure: Nothing to disclose.

Acknowledgements

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.