Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency

Study Overview
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Brief Summary
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Participants wanted for study of mevalonate kinase deficiency (MKD), mevalonic aciduria, or hyperimmunoglobulinemia with periodic fever syndrome (HIDS). Patients with MKD (mevalonic aciduria or hyperimmunoglobulinemia with periodic fever syndrome (HIDS)) may be eligible for a research study conducted at Oregon Health & Science University (OHSU) in Portland, Oregon USA. The purpose of the study is to find out more about how these diseases affect body chemistry and health. The researchers also want to find out how cholesterol in the diet affect blood cholesterol and how the body handles cholesterol. This is a short-term and long-term dietary study. The long-term goal of this research is to see if controlling dietary cholesterol can decrease any of the symptoms of the diseases. The study could involve up to 12 one-week admissions to OHSU over the course of 5 years.

Detailed Description
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Participants are admitted to the clinical research center for up to a week per visit. Additional visits at least yearly encouraged. During the week we measure such things as cholesterol absorption, sterol and bile acid synthesis, mevalonate and mevalonate shunt products, isoprenoids, fatty acids, leukotrienes, plasma cholesterol and other sterol levels. Also, the effects of altering dietary cholesterol on plasma 24-S OH-cholesterol, a measure of brain cholesterol turnover, will be evaluated. Studies of body composition/ metabolism/ growth, development, behavior, sleep, feeding, hearing and vision will be carried out to document the phenotype and determine if dietary intervention may be helpful. The objective of the study is to characterize the metabolic and phenotypic consequences of MKD and study the effects of altering dietary cholesterol in MKD. We hypothesize that some of the phenotypic effects of MKD are due to altered cholesterol metabolism, but that the phenotype is predominantly due to derangements in isoprenoid metabolism.

Official Title
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Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency

Conditions
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Mevalonic Aciduria, Mevalonate Kinase Deficiency, Immune System Diseases, Periodic Fever Syndromes, Hereditary, Lipid Metabolism, Inborn Errors

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have documented mevalonate kinase deficiency, mevalonic aciduria, or HIDS Must be willing to participate in most research procedures Exclusion Criteria: Unable or unwilling to participate in most research procedures
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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effects of dietary cholesterol changes in MKD on cholesterol and related synthetic pathways | blood levels of cholesterol | December 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define genotype, phenotype and response to dietary cholesterol. Determine genotype-therapy correlations. | Gene Mutations - 7-dehydrocholesterol levels | December 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholesterol defects, Mevalonic Aciduria, Mevalonate Kinase Deficiency, HIDS, Hyperimmunoglobulinemia with periodic fever syndrome, MKD, Lipid Metabolism, Inborn Errors, Periodic Fever Syndromes, hereditary, mevalonic acid, mevalonate kinase, cholesterol, dietary, Hyper IgD, Multiple malformations, Fever