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General Information About Hermansky-Pudlak Syndrome

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Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder that manifests as oculocutaneous albinism, bleeding due to platelet abnormalities, and lysosomal accumulation of ceroid lipofuscin, which can impact a number of organs but most commonly results in dysfunction of the colon, lungs, and kidneys. The severity and course of the disease varies considerably among individual patients.

HPS was first described in Czechoslovakia by Frantisek Hermansky and Paulus Pudlak in 1959. Since then, cases have been reported throughout the world and the condition is thought to be particularly prevalent in Switzerland, Japan, and Puerto Rico, with an estimated prevalence in the latter of 1 in 1800 individuals. Multiple mutations have been associated with HPS, including abnormalities in HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and BLOC1S6. A number of subtypes of the syndrome are described.

The diagnosis of HPS is most often considered in patients who present with hypopigmentation of the skin and hair as well as characteristic eye findings, including visual impairment, nystagmus, reduced pigmentation of the iris and retina, foveal hypoplasia, and increased crossing of the optic nerve fibers. Examination of platelets via electron microscopy in HPS reveals the absence of dense bodies. The platelet count and coagulation factor activities are normal but the bleeding time is prolonged because of abnormal platelet function. Ceroid lipofuscin, a yellow, autofluorescent, amorphous lipid-protein complex, can be demonstrated in urinary sediment and some tissues but is not generally useful diagnostically.

A number of clinical features are characteristic of HPS, including:

Albinism, visual impairment, nystagmus, strabismus, and photophobia.

Easy bruising and bleeding.

Interstitial lung disease

Inflammatory bowel disease, with granulomatous colitis

No specific therapy is available for HPS. Corrective lenses and use of low vision aids are generally required, as are measures to limit actinic exposure of the eyes and skin. DDAVP and platelet transfusion may be required during episodes of significant bleeding. Interstitial lung disease may require long-term oxygen therapy and lung transplantation, and colitis may respond to treatment with corticosteroids , infliximab, or other anti-inflammatory agents. Genetic counseling is indicated for patients and family members. Immunizations should be kept current, and aspirin and NSAIDS avoided.

The Hermansky-Pudlak Syndrome Network is a valuable resource for patients with the condition as well as for physicians and scientists with an interest in it. The HPSN website (https://www.hpsnetwork.org/en) contains valuable resources including medical information, community connections, and news about recent scientific developments and upcoming conferences related to the conditions.

Bibliography:

  1. Furuhashi K, Enomoto N, Fujisawa T, Hashimoto D, Inui N, Nakamura Y, Suda T. Hermansky-Pudlak syndrome with nonspecific interstitial pneumonia. Intern Med. 2014;53(5):449-53.
  2. Mora AJ, Wolfsohn DM. The management of gastrointestinal disease in Hermansky-Pudlak syndrome. J Clin Gastroenterol. 2011 Sep;45(8):700-2.
  3. Pierson DM, Ionescu D, Qing G, Yonan AM, Parkinson K, Colby TC, Leslie K. Pulmonary fibrosis in Hermansky-Pudlak syndrome. A case report and review. Respiration. 2006;73(3):382-95.
  4. Schneier AJ, Fulton AB. The Hermansky-Pudlak syndrome: clinical features and imperatives from an ophthalmic perspective. Semin Ophthalmol. 2013 Sep-Nov;28(5-6):387-91.
  5. Seward SL Jr, Gahl WA. Hermansky-Pudlak syndrome: health care throughout life. Pediatrics. 2013 Jul;132(1):153-60.
  6. Wei AH, Li W. Hermansky-Pudlak syndrome: pigmentary and non-pigmentary defects and their pathogenesis. Pigment Cell Melanoma Res. 2013 Mar;26(2):176-92.
  7. Wei ML. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006 Feb;19(1):19-42.
  8. Young LR, Gulleman PM, Bridges JP, Weaver TE, Deutsch GH, Blackwell TS, McCormack FX. The alveolar epithelium determines susceptibility to lung fibrosis in Hermansky-Pudlak syndrome. Am J Respir Crit Care Med. 2012 Nov 15;186(10):1014-24.

Four Facts About Hermansky-Pudlak Syndrome
  1. Hermansky-Pudlak Syndrome (HPS) causes a genetic pulmonary fibrosis in gene types 1, 2 and 4.

  2. HPS is a type of albinism, thus all patients with HPS have nystagmus and most are legally blind. The phenotype of HPS can vary widely, from a very fair complexion to olive skin and dark hair and eyes.

  3. To date, the HPS Network is aware of 14 successful lung transplants.

  4. Esbriet is a medication that has been studied in clinical trials involving patients with HPS.