Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

Study Overview
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Brief Summary
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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>

Detailed Description
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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.

Official Title
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Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

Conditions
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Hermansky-Pudlak Syndrome (HPS)

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HPS<br>HPS patients of any gender and ethnicity age 1-80 years | |
| HPS Symptom Questionnaire<br>Includes both patients and family members or caregivers. | |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Albinism, Platelet Storage Pool Deficiency, Metabolic Disease, Pulmonary Fibrosis, Inflammatory Bowel Disease, Natural History