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Dermatologic Manifestations of Hermansky-Pudlak Syndrome Workup

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

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 DBs (referred to as chocolate chips) in the platelets is indicative of this syndrome. Note the following:

  • Drops of platelet-rich plasma separated from blood are placed on Formvar microscope grids for 1 minute. Next, they are rinsed by passing them through drops of distilled water. Fluid is removed from the grid edges with filter paper, and they are air dried and inserted into the electron microscope.
  • DBs are inherently electron opaque and easily visualized in whole mount preparations. They are spherical in form, and, although variable in size, they differ significantly from other electron-dense structures in platelets, including clusters, chains, relatively dense alpha granules, and giant lysosomes.
  • The uranaffin reaction of Richards and DaPrada deposits uranium salts in the inner half of the DB membrane and can help distinguish DBs from other organelles, but it is not useful for whole mount preparations.
  • Determining the number of DBs in platelets before and after exposure to thrombin provides a reasonable estimate of secretable DBs in platelets containing opaque, nondense body structures. The ultrastructure of ceroid-lipofuchsin inclusions in macrophages in bone marrow, gut, and other tissues can be helpful, but the absence of DBs 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 reference range. Many patients with Hermansky-Pudlak syndrome have reduced von Willebrand factor activity in their platelets. Patients with Hermansky-Pudlak syndrome have been reported to 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.[31] 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.[32]

Because of a propensity to bleed, 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

Because patients have impaired vision, their 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. Visual acuity testing is also useful.

In children with Hermansky-Pudlak syndrome, because their vision can be impaired in a fashion that affects their ability to learn, 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.



Biopsy should immediately be performed on new skin growths because the potential for the development of skin cancers in these patients is great.


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[33] 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.

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.

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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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