Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

• ClinicalTrials.gov Identifier: NCT00001456
• Recruitment Status: Recruiting
• First Posted: November 4, 1999
• Last Update Posted: May 26, 2023
• Sponsor: National Human Genome Research Institute (NHGRI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Study Description

Brief Summary:

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>...

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 600 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
• Actual Study Start Date: November 6, 1995

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Natural History [ Time Frame: Ongoing ]
   The natural history of Hermansky-Pudlak Syndrome (HPS)

Eligibility Criteria

• Ages Eligible for Study: 1 Month and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

• 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.

Contacts and Locations

Contacts

Contact: Wendy J Introne, M.D.; (301) 451-8879; wi2p@nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Human Genome Research Institute (NHGRI)

Investigators

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

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Human Genome Research Institute (NHGRI)
• ClinicalTrials.gov Identifier: NCT00001456
• Other Study ID Numbers: 950193; 95-HG-0193
• First Posted: November 4, 1999
• Last Update Posted: May 26, 2023
• Last Verified: January 31, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: .pending

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):

Albinism; Platelet Storage Pool Deficiency; Metabolic Disease; Pulmonary Fibrosis; Inflammatory Bowel Disease; Natural History

Additional relevant MeSH terms:

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