Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is an inherited disease which results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin).

The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The major complication of the disease is pulmonary fibrosis and typically causes death in patients ages 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS.

The purpose of this study is to perform research into the medical complications of HPS and begin to understand what causes these complications. Researchers will clinically evaluate patients with HPS of all ethnic backgrounds. They will obtain cells, blood components (plasma), and urine for future studies. Genetic tests (mutation analysis) to detect HPS-causing genes will also be conducted.<TAB>

Study Overview

• Status: Recruiting
• Conditions: Hermansky-Pudlak Syndrome (HPS)

Detailed Description

Study Description:

Hermansky-Pudlak syndrome is a rare autosomal recessive disease consisting of oculocutaneous albinism, a platelet storage pool defect and, in some patients, lysosomal accumulation of ceroid lipofuscin. Other manifestations include pulmonary fibrosis (often fatal in the fourth or fifth decade), chronic granulomatous colitis and, rarely, renal involvement or cardiomyopathy. The purpose of this protocol is to evaluate individuals with HPS, perform mutation analysis for known HPS-causing genes, search for variants in other genes responsible for HPS, and obtain specimens to analyze basic mechanisms of HPS.

Objectives:

Primary Objective: Assess the clinical severity of HPS, to study the natural history of disease, to identify variants in genes associated with HPS, and to investigate basic defect(s) in HPS and mechanisms of disease.

Study Population:

All participants will be persons with HPS, or their family members, aged 1-80 years. The enrollment ceiling is 600; we estimate that approximately 200 subjects will participate only in the HPS Symptom Questionnaire. Family members who are caregivers of affected individuals, including children, may be invited to participate in the HPS Symptom Questionnaire to provide responses related to their affected relative. We anticipate enrolling 2-10 new subjects per year under this protocol.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Wendy J Introne, M.D.; Phone Number: (301) 451-8879; Email: wi2p@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HPS patients of any sex and ethnicity age 1-80 years

Description

• INCLUSION CRITERIA

Persons with HPS or family members who are their caregivers aged 1-80 years are eligible to enroll in this protocol. The diagnosis of HPS is based upon a paucity or deficiency of platelet dense bodies on whole mount electron microscopy or the identification of pathogenic variants in HPS genes by genetic testing. Some persons who have not been diagnosed with HPS may be admitted to the protocol based upon the presence of albinism and a platelet storage pool deficiency.

Subjects participating only in the HPS Symptom Questionnaire will be at least 18 years of age.

EXCLUSION CRITERIA

Pregnant women and adults who are unable to provide consent are excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
HPS Symptom Questionnaire; Includes both patients and family members or caregivers.
HPS; HPS patients of any sex and ethnicity age 1-80 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural History	The natural history of Hermansky-Pudlak Syndrome (HPS)	Ongoing

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Wendy J Introne, M.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

General Publications

• Han CG, O'Brien KJ, Coon LM, Majerus JA, Huryn LA, Haroutunian SG, Moka N, Introne WJ, Macnamara E, Gahl WA, Malicdan MCV, Chen D, Krishnan K, Gochuico BR. Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel HPS6 missense variant. Am J Med Genet A. 2018 Dec;176(12):2819-2823. doi: 10.1002/ajmg.a.40514. Epub 2018 Oct 4.
• El-Chemaly S, Cheung F, Kotliarov Y, O'Brien KJ, Gahl WA, Chen J, Perl SY, Biancotto A, Gochuico BR. The Immunome in Two Inherited Forms of Pulmonary Fibrosis. Front Immunol. 2018 Jan 31;9:76. doi: 10.3389/fimmu.2018.00076. eCollection 2018.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 1995

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimated): November 4, 1999

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 5, 2026
• Last Verified: September 4, 2026

More Information

Terms related to this study

• Keywords: Natural History; Inflammatory Bowel Disease; Metabolic Disease; Pulmonary Fibrosis; Albinism; Platelet Storage Pool Deficiency
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Intestinal Diseases; Respiratory Tract Diseases; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Eye Diseases; Hematologic Diseases; Skin Diseases; Gastroenteritis; Eye Diseases, Hereditary; Blood Coagulation Disorders; Hypopigmentation; Pigmentation Disorders; Lung Diseases, Interstitial; Hemorrhagic Disorders; Skin Diseases, Genetic; Blood Platelet Disorders; Amino Acid Metabolism, Inborn Errors; Blood Coagulation Disorders, Inherited; Fibrosis; Albinism, Oculocutaneous; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Pulmonary Fibrosis; Metabolic Diseases; Inflammatory Bowel Diseases; Hermanski-Pudlak Syndrome; Albinism; Platelet Storage Pool Deficiency
• Other Study ID Numbers: 950193; 95-HG-0193

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: pending

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No