Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome
Condition: Smith-Lemli-Opitz Syndrome
MeSH terms: Cleft Palate; Hypertelorism; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Syndrome
Intervention: Egg yolk preparation with cholesterol; Egg substitute, without cholesterol
Intervention description: Egg yolk preparation with cholesterol; Placebo control. Egg substitute, without cholesterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 13.0
Sex: All
Minimum age: 4 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: SLOS; RSH syndrome; ABC Checklist; Cholesterol supplementation; Egg yolk; Smith-Lemli-Opitz Syndrome

Summary:

      This 10-week study will evaluate and compare behavior changes in children with
      Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who
      are not on cholesterol supplementation. SLOS is a genetic disorder that affects the
      development of children both before and after birth. An enzyme deficiency in these children
      results in low levels of cholesterol, which can cause a variety of birth defects and
      behavioral problems. Typical abnormal physical features of patients include a small head,
      drooping eyelids, small upturned nose, small chin, cleft palate, heart defects, and extra
      fingers or toes.

      Children between 5 and 17 with mild SLOS who do not have a history of egg allergy or
      intolerance may be eligible for this study. Candidates are screened with a questionnaire
      about the patient's age, genotype (if known), sterol levels, symptoms, current treatment and
      medical history.

      Children participate in two 2-week study phases. Between the study phases the children will
      take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in
      patients in SLOS studies at NIH. In the study phases, the participants are randomly assigned
      to take either egg yolk or an egg yolk substitute, such as Egg Beaters, that does not contain
      cholesterol. The study is done at the participant's home, and the cholesterol supplementation
      and egg/egg substitute are sent to the home each day with instructions on how to take them.

      The caretakers can stop the study phases after four days if behavior problems occur.

      The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior
      Checklist. The questionnaire is designed to assess the effects of treatment in mentally
      impaired persons.
    

Eligibility criteria:

        Inclusion

          1. This study will include pediatric patients, ages 4-17 years old with a biochemical
             diagnosis of Smith-Lemli-Opitz Syndrome (SLOS).

          2. Only mild and classical patients will be enrolled.

          3. This study will be open to include SLOS patients regardless of whether or not they are
             participating in another NIH protocol.

        Exclusion

          1. Patients with a history of egg allergy or intolerance will be excluded from this
             study.

          2. Subjects must be well enough to be in a home setting.

          3. Patients participating in our simvastatin protocol (03-CH-3225) will be excluded from
             this study.