eMedicine Specialties > Dermatology > Diseases of Pigmentation

Hermansky-Pudlak Syndrome: Differential Diagnoses & Workup

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
Coauthor(s): Ann M Johnson, MD, Pediatric Radiology Fellow, Department of Radiology, The Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Feb 14, 2008

Differential Diagnoses

Albinism
Chediak-Higashi Syndrome

Workup

Laboratory Studies

  • Genetic testing for the HPS1 gene, which most commonly occurs in Puerto Ricans, exists. A company called Gene D can perform DNA screening for the 16–base pair duplication found in this variation of the syndrome.
  • 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.
    • 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 HPS.
  • Standard blood tests (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT], platelet count, bleeding time) do not identify the platelet defect in HPS.
    • Bleeding time of patients with HPS varies from 6-20 minutes. As many as 25% of patients with HPS have bleeding times within the reference range.
    • Many patients with HPS have reduced von Willebrand factor activity in their platelets. Patients with HPS 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 HPS have tyrosine-positive albinism.
    • Clinical correlation is necessary because some patients with HPS 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 HPS.16 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 HPS had abnormalities on high-resolution CT scans.17
  • Because of a propensity to bleed, patients with HPS 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 HPS, because their vision can be impaired in a fashion that affects their ability to learn, educational and intellectual testing should be performed.
  • Patients with HPS 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 HPS.

Procedures

  • 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 al18 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 HPS. Conversely, persons with HPS have lower macular volumes compared with the general population, perhaps because of a loss of retinal nuclear layers in these patients.

More on Hermansky-Pudlak Syndrome

Overview: Hermansky-Pudlak Syndrome
Differential Diagnoses & Workup: Hermansky-Pudlak Syndrome
Treatment & Medication: Hermansky-Pudlak Syndrome
Follow-up: Hermansky-Pudlak Syndrome
Multimedia: Hermansky-Pudlak Syndrome
References
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References

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Further Reading

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Keywords

Hermansky-Pudlack syndrome, HPS, oculocutaneous albinism, lysosomal ceroid storage

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Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Ann M Johnson, MD, Pediatric Radiology Fellow, Department of Radiology, The Children's Hospital of Philadelphia
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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