Study of Inborn Errors of Cholesterol Synthesis and Related Disorders

Study Overview
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Brief Summary
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This study will investigate the cause and medical problems associated with a group of genetic disorders known as inborn errors of cholesterol synthesis, in which the body does not produce cholesterol. People with this disorder may have birth defects and learning and behavioral problems. People with an inborn error of cholesterol synthesis and related disorders, including Smith-Lemli-Opitz syndrome, lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia, CHILD syndrome, Greenberg dysplasia, and some cases of Antley-Bixler syndrome, may be eligible for this study. People who are carriers of the disorders also may enroll. Participants and family members will provide blood and urine samples, as well as other tissue samples collected during medically indicated procedures such as biopsy or surgery. These tissues may include, for example, gallstones, cataracts, cerebrospinal fluid, amniotic fluid, lymph tissue, and DNA samples. In rare instances, a skin biopsy may be requested to aid in establishing a diagnosis. Medical information will also be gathered from medical records, photographs, and X-rays.

Detailed Description
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It is known that inborn errors of cholesterol synthesis give rise to human malformation/cognitive impairment syndromes. Smith-Lemli-Opitz syndrome is the prototypical example of a post-squalene inborn error of metabolism; however, this group of disorders now includes lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia (CDPX2), CHILD syndrome, HEM dysplasia, and some cases of Antley-Bixler syndrome (1-3). Due to the extremely rare occurrence of some of these disorders, the full phenotypic spectrum has yet to be defined. Cholesterol transport in cells can also cause a disorder known as Niemann-Pick Disease type C (NPC). NPC belongs to a group of disorders known as lysosomal storage disorders. The purpose of this protocol is to 1) allow for the collection of biomaterial and medical information that can be studied to gain insight into the pathological processes; 2) allow for the collection of DNA and medical information from individuals who have a phenotypic resemblance to known disorders of cholesterol synthesis, lysosomal storage disorders or individuals who may be carriers of these disorders.

Official Title
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Investigations Into Inborn Errors of Cholesterol Synthesis and Related Disorders

Conditions
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Cholesterol Metabolism, Lysosomal Storage Disease

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Subjects will be eligible for this study if they have or are suspected to have an inborn error of cholesterol synthesis or if they are related to a proband with a suspected inborn error of cholesterol synthesis. No exclusions will be made based on gender, ethnicity or age.
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 |
| --- | --- |
| normal subjects<br>subjects in whom no disorder of cholesterol is suspected related to affected individuals | |
| subjects suspected of cholesterol disorder<br>subjects in whom a disorder of cholesterol metabolism is suspected | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sample collection | collect sample to study rare manifestations or disease | event driven upon enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inborn Error of Cholesterol Synthesis, Cholesterol, Lysosomal Storage, Natural History, Inborn Errors of Cholesterol Synthesis, Smith-Lemli-Optiz Syndrome, Lathosterolosis, Desmosterols, CHILD Syndrome, Greenberg Dysplasia, X Linked Dominant Chrondrodysplasia