Rare Lung Disease

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General Information

Rare Lung Disease Week

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease that is most prevalent in the northwest section of Puerto Rico, where the frequency is 1 in 1800 due to a founder mutation.  However, Hermansky-Pudlak Syndrome has now been reported worldwide, and more than 1100 individuals have registered with Hermansky-Pudlak Syndrome Network (www.hpsnetwork.org).  Symptoms of Hermansky-Pudlak Syndrome include oculocutaneous albinism (OCA), bleeding due to platelet dysfunction, and colitis and highly penetrant pulmonary fibrosis in some groups of young adults.  There are now 9 reported genetically distinct subtypes of Hermansky-Pudlak Syndrome (denoted HPS-1-9), but interstitial lung disease and pulmonary fibrosis have only been observed in subtypes HPS-1, HPS-2, and HPS-4.  Hermansky-Pudlak Syndrome diagnostic criteria include tyrosinase-positive OCA and a specific platelet storage pool deficiency.  Standard laboratory blood test results are not sufficient to diagnosis of Hermansky-Pudlak Syndrome, and examination of platelet dense granules by electron microscopy must be performed by an experienced lab.  Since pulmonary fibrosis has only been observed in patients with HPS-1, HPS-2, and HPS-4, it is clinically important to know the HPS subtype.

Nonproductive cough and progressive shortness of breath on exertion are the most common presenting pulmonary symptoms. Hermansky-Pudlak Syndrome pulmonary fibrosis exhibits some clinical and radiographic features found in idiopathic pulmonary fibrosis (IPF), but occurs at a younger age.  Lung histology from affected Hermansky-Pudlak Syndrome patients also shares some similarities to the patterns observed in IPF, including hyperplastic type II alveolar epithelial cells (AECs).  However, other features of Hermansky-Pudlak Syndrome pulmonary fibrosis are not typical for idiopathic pulmonary fibrosis, including the presence of irregular lamellar bodies and lipid accumulation in AECs, and the presence of alveolar inflammation and alveolar macrophage activation.  Diagnosis of pulmonary fibrosis is made by chest high resolution CT scan, as lung biopsy is generally contraindicated because of bleeding complications.  The natural history of pulmonary fibrosis in HPS has been reported as variable but universally progressive, with mortality commonly occurring typically in the 4th-5th decades of life, and with an approximate survival of two years after forced vital capacity (FVC) reaches 50% of predicted values. However, the age of death has ranged from 26-61 years, and decline in FVC is not uniform.  Emerging therapies for Idiopathic Pulmonary Fibrosis (IPF) may also have a role in treating HPS patients who have patterns of pulmonary fibrosis similar to that seen in IPF.  Lung transplantation has also helped a small number of patients.

Bibliography:

Hermansky-Pudlak syndrome: health care throughout life. Seward SL Jr, Gahl WA. Pediatrics. 2013 Jul;132(1):153-60. doi: 10.1542/peds.2012-4003. Epub 2013 Jun 10. Review. PMID: 23753089

Congenital disorders associated with platelet dysfunctions. Nurden P, Nurden AT. Thromb Haemost. 2008 Feb;99(2):253-63. doi: 10.1160/TH07-09-0568. Review. PMID:  18278172

Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Kropski JA, Lawson WE, Young LR, Blackwell TS. Dis Model Mech. 2013 Jan;6(1):9-17.


Four Facts About Hermansky-Pudlak Syndrome

  1. Hermansky-Pudlak Syndrome (HPS) gene causes pulmonary fibrosis in gene types 1, 2 and 4; therefore, it can be followed prior to patient reported symptoms. New research centers opening in the Rare Lung Disease Consortium, part of ORD/NCATS, will begin to study the PFT’s of children.

  2. Hermansky-Pudlak Syndrome is characterized by a platelet bleeding disorder. In the past, the standard of care supported platelet transfusions to prevent bleeding during surgical and dental procedures. Because of the formation of antibodies that can cause difficulty matching lungs for transplant, the recommendation is to keep platelets on standby until needed rather than transfusing liberally.

  3. Postoperatively, platelets and medications that enhance clotting are routinely prescribed after surgeries. Careful use of this therapy with attention to dosing and timing is necessary as DVT’s and unwanted clotting have occurred from possible overcorrection.

  4. Recently published research in the Journal of Genetic Counseling reported in an article “The Misdiagnosis of a Rare Disease: The Journey to a Hermansky-Pudlak Syndrome Diagnosis” that the mean number of years from first symptom to diagnosis was sixteen, and 76 percent of individuals were initially misdiagnosed.