Study of Inborn Errors of Cholesterol Synthesis and Related Disorders

• ClinicalTrials.gov Identifier: NCT00046202
• Recruitment Status: Recruiting
• First Posted: September 23, 2002
• Last Update Posted: February 11, 2021
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Tracking Information

• First Submitted Date: September 21, 2002
• First Posted Date: September 23, 2002
• Last Update Posted Date: February 11, 2021
• Actual Study Start Date: October 9, 2002
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: March 23, 2019)

sample collection [ Time Frame: event driven upon enrollment ]

collect sample to study rare manifestations or disease

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Inborn Errors of Cholesterol Synthesis and Related Disorders
• Official Title: Investigations Into Inborn Errors of Cholesterol Synthesis and Related Disorders

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: Over the past 15 years, it has become clear that inborn errors of cholesterol synthesis give rise to human malformation/mental retardation 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.
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Other
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients and their relatives, samples from biorepositories

Condition

• Lysosomal Storage Disease
• Cholesterol Metablism

• Intervention: Not Provided

Study Groups/Cohorts

• normal subjects
  subjects in whom no disorder of cholesterol is suspected related to affected individuals
• subjects suspected of cholesterol disorder
  subjects in whom a disorder of cholesterol metabolism is suspected

Publications *

• Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet. 2000 May;37(5):321-35. Review.
• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2016): 1000
• Original Enrollment (submitted: June 23, 2005): 300
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Simona E Bianconi, M.D.; (301) 496-8597; simona.bianconi@nih.gov

Contact: Forbes D Porter, M.D.; (301) 435-4432; fdporter@mail.nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00046202
• Other Study ID Numbers: 020311; 02-CH-0311
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
• Study Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Forbes D Porter, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: January 26, 2021