Study of Inborn Errors of Cholesterol Synthesis and Related Disorders

Investigations Into Inborn Errors of Cholesterol Synthesis and Related Disorders

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.

Study Overview

• Status: Recruiting
• Conditions: Lysosomal Storage Disease; Cholesterol Metabolism

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Forbes D Porter, M.D.; Phone Number: (301) 435-4432; Email: fdporter@mail.nih.gov
• Study Contact Backup: Name: Nicole M Farhat, C.R.N.P.; Phone Number: (301) 496-9135; Email: nicole.farhat@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Convenience sampling: affected patients and their relatives, samples from biorepositories

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2002

Study Registration Dates

• First Submitted: September 21, 2002
• First Submitted That Met QC Criteria: September 21, 2002
• First Posted (Estimated): September 23, 2002

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: September 22, 2023

More Information

Terms related to this study

• Keywords: Cholesterol; Natural History; Lysosomal Storage; Inborn Error of Cholesterol Synthesis; Inborn Errors of Cholesterol Synthesis; Smith-Lemli-Optiz Syndrome; Lathosterolosis; Desmosterols; CHILD Syndrome; Greenberg Dysplasia; X Linked Dominant Chrondrodysplasia
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases
• Other Study ID Numbers: 020311; 02-CH-0311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: .Data will be shared in aggregate related to the disorders represented by accrual.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No