Hermansky-Pudlak Syndrome

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General Information


Hermansky-Pudlak Syndrome (HPS) is a rare genetic disorder that has autosomal recessive inheritance.  HPS has been reported worldwide but is concentrated in Puerto Rico, where an estimated ~50% of cases are diagnosed.  Clinical features include oculocutaneous albinism, platelet dysfunction resulting in bleeding as well as a Crohn’s-like colitis in some HPS patients. Pulmonary fibrosis occurs in subtypes 1,2 and 4. There are 10 different forms of the disease that have been described and each are due to different mutations in HPS associated genes.  The HPS-1 form is the most common and associated with lung disease. HPS-2 and HPS-4 also have severe phenotypes. The proteins encoded by HPS genes are involved in the biogenesis of lysosome-related organelle complexes (BLOCs).  These lysosome-related organelles (LROs) are involved in cellular trafficking of proteins in the cell including to melanosomes and platelet dense granules.  How these trafficking defects relate to the lung fibrosis aspects of the disease remains unclear and is a part of current ongoing research.  Investigators hypothesize that HPS mutations result in alveolar epithelial cell dysfunction, which then drives lung fibrosis through effects on macrophage and fibroblast activity. Naturally-occurring and transgenic animals with HPS mutations are an actively utilized tool to understand disease pathogenesis.  It is hoped that by using these models as well as tissue from patients with HPS mutations, targeted therapies can be developed to treat this condition. 

Through studies conducted at the National Institutes of Health (NIH) since 1995, many significant advances have been made in HPS, including identifying the genetic basis. However, there are no FDA-approved therapies for HPS pulmonary fibrosis.  Lung transplantation has been performed successfully for HPS.  Because of the recognizable clinical features of HPS, it is hoped that preventative approaches and/or early disease treatment strategies can be developed. 

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

  2. Hermansky-Pudlak Syndrome involves albinism, but pigmentation can vary widely. Not everyone with HPS has fair skin and blonde hair.

  3. Patients with Hermansky-Pudlak Syndrome have nystagmus. Sometimes it can be subtle.

  4. Hermansky-Pudlak Syndrome involves a bleeding disorder. PT and PTT tests are typically normal. The bleeding in HPS is very treatable.