7001: Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation
The purpose of this study is to learn as much as possible about Smith-Lemli-Opitz Syndrome (SLOS) by following a large group of affected children and adults over time. In this study, we will measure cholesterol and other similar chemicals in blood and urine, evaluate development and behavior, do limited medical evaluation, and carry out brain imaging studies.
This study will help researchers:
- learn more about what causes SLOS and how SLOS changes with age,
- note differences in features of SLOS among those affected,
- evaluate the effect of giving extra cholesterol in this condition, and
- develop ways to evaluate whether treatments developed in the future will be helpful.
Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.
Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol production by the body. It is caused by changes in the DHCR7 gene, which is the blueprint for an enzyme called 7-dehydrocholesterol- delta7-reductase. This enzyme is necessary for the production of cholesterol by the body. People affected by SLOS often have malformations of major organs, slow growth, feeding difficulties, and intellectual disability or learning problems.
Because patients with SLOS cannot make enough cholesterol, it has been proposed that cholesterol supplementation (either with egg yolk or liquid suspensions of cholesterol) could help improve the symptoms of the disease. However, despite the widespread use of cholesterol supplementation, it is still not known whether it works or not. The study will try to provide an answer to this question by studying the disease and its progression while patients are receiving cholesterol.
The clinical features of SLOS are thought to be related to low cholesterol and buildup of toxic cholesterol precursors (substances from which cholesterol is formed). But how exactly low cholesterol and toxic precursors contribute to the disease is poorly understood. This knowledge is critically important because it should help discover new therapeutic targets and develop treatments of the disease in the long run. The study will try to fill this gap with a comprehensive clinical and biochemical testing of the study participants over the course of several years.
Last, a limitation of previous SLOS research studies has been their low number of participants. This is understandable because SLOS is a rare diseases and few research groups are working on it. However, in order to fully understand the disease, researchers need to study as many patients as possible. This study is unique in that it is run by a network of several highly specialized clinical research sites across the country. Having several sites involved increases the researchers' ability to recruit and study large number of patients, and centralizes patients' information in a comprehensive SLOS clinical registry. This registry will be key to identify markers for diagnostic testing, screening and measuring outcomes in future studies of treatment.
The goal of the study is to describe the SLOS disease progression and identify correlations between clinical, biochemical and physiological features of the disease in patients receiving cholesterol supplementation.
The main research question is: does cholesterol supplementation improve I.Q. and behavior?
Other research questions include:
- Does cholesterol supplementation change the whole body cholesterol content in patients with SLOS? and
- Does cholesterol supplementation change brain development as shown by MRI?
About this Study
Type of study: Natural history, interventional (because to participate, patients must be on cholesterol supplementation)
Length of study: Four years (2010 - 2014 and beyond)
Number of participants: At least 30
Participants are asked to come once a year to the research centers for a 3 to 5 day inpatient visit. During this visit, they will undergo a comprehensive clinical and metabolic evaluation that includes:
- blood draws (collection of blood from a vein for laboratory testing),
- urine collections,
- feeding / swallowing / oral motor assessments,
- behavioral and developmental testing,
- brain MRI
- dietary cholesterol intake assessment.
- hearing and vision assessment
Changes in learning or intellectual outcomes over time will be correlated with cholesterol intake, biochemical markers, and changes in whole body cholesterol content.
To be eligible for this study, patients must:
- have a confirmed diagnosis of SLOS and
- be able to travel to a STAIR site and participate in study procedures.
Anyone meeting these eligibility criteria can participate. This includes:
- Patients currently followed at STAIR sites and already enrolled in research studies
- Patients referred to STAIR by their physicians, and
- Patients who are not currently participating in any research but directly contact STAIR sites.
How to participate
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda
Sandra K. Conley, RN, MS, CPNP
- University of Nebraska Medical Center, Omaha
Machelle Zink, RN
- Cincinnati Children's Hospital Medical Center, Cincinnati
- Oregon Health & Science University, Portland
Sharon Butcher, RN, MSN, CPNP
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh
Nancy Perrott Taylor, RD, LDN
Study Coordinator, Metabolic Dietitian
Phone: (412) 692-3150
Be notified when new locations open for this study!
Join the Contact Registry for Smith-Lemli-Opitz Syndrome