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

Hermansky-Pudlak syndrome (HPS) 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. There exist 10 different genes known to cause HPS, but only HPS-2 and HPS-10 have a basic defect whose mechanism is known, i.e., defective subunits of a coat protein, adaptor complex-3, responsible for intracellular vesicle formation. HPS-1 is a severe genetic type common in northwest Puerto Rico, and HPS-3 is a milder one seen in central Puerto Rico. HPS-4 resembles HPS-1 in severity; HPS-5 and HPS-6 resemble HPS-3 in severity. HPS-7, HPS-8, and HPS-9 are extremely rare and have not been fully characterized. 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.

• 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 gender and ethnicity age 1-80 years

Description

• INCLUSION CRITERIA:

Subjects with HPS age 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 subjects 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.

Most female subjects who participate in the Obstetrics/Gynecology Questionnaire will be enrolled in the protocol.

Subjects with HPS or family members who are their caregivers participating in the HPS Symptom Questionnaire will be at least 18 years of age. These subjects will enroll in the protocol and will provide written consent.

EXCLUSION CRITERIA:

Infants under age one year are excluded because there is generally no urgency for a very early diagnosis and care is more readily provided to older infants at the Clinical Center.

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

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): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: January 9, 2024

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; Metabolic Diseases; Skin Diseases; Eye Diseases; Disease; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Hemorrhagic Disorders; Genetic Diseases, Inborn; Skin Diseases, Genetic; Eye Diseases, Hereditary; Blood Coagulation Disorders; Metabolism, Inborn Errors; Blood Platelet Disorders; Amino Acid Metabolism, Inborn Errors; Pigmentation Disorders; Hypopigmentation; Albinism; Albinism, Oculocutaneous; Platelet Storage Pool Deficiency; Syndrome; Hermanski-Pudlak Syndrome
• 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