Study of Inborn Errors of Cholesterol Synthesis and Related Disorders

NCT ID: NCT00046202

Last Updated: 2025-12-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 342 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2002-10-09

Brief Summary

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

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.

Conditions

Lysosomal Storage Disease; Cholesterol Metabolism

Keywords

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

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

normal subjects

subjects in whom no disorder of cholesterol is suspected related to affected individuals

No interventions assigned to this group

subjects suspected of cholesterol disorder

subjects in whom a disorder of cholesterol metabolism is suspected

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Forbes D Porter, M.D.

Role: PRINCIPAL_INVESTIGATOR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet. 2000 May;37(5):321-35. doi: 10.1136/jmg.37.5.321.

Reference Type: BACKGROUND

PMID: 10807690 (View on PubMed)

Nwokoro NA, Wassif CA, Porter FD. Genetic disorders of cholesterol biosynthesis in mice and humans. Mol Genet Metab. 2001 Sep-Oct;74(1-2):105-19. doi: 10.1006/mgme.2001.3226.

Reference Type: BACKGROUND

PMID: 11592808 (View on PubMed)

Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW. Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia. Am J Med Genet. 2002 Jun 15;110(2):95-102. doi: 10.1002/ajmg.10510.

Reference Type: BACKGROUND

PMID: 12116245 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2002-CH-0311.html

NIH Clinical Center Detailed Web Page

Other Identifiers

020311

Identifier Type: -

Identifier Source: org_study_id

02-CH-0311

Identifier Type: -

Identifier Source: secondary_id