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Date of Graduation

8-2003

Degree Type

Capstone Project (On-Campus Access Only)

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Jon Gietzen, PA-C

Abstract

Background Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol metabolism characterized by multiple congenital malformations, mental retardation, and growth failure. Affected individuals exhibit deficiency of 7-dehydrocholesterol-delta 7-reductase, and thus show reduced cholesterol and excess cholesterol intermediates. Dietary cholesterol supplementation is a potentially beneficial treatment currently under investigation.

Method We evaluated growth and the effects of dietary cholesterol on growth in 17 subjects (7 male, 10 female) with SLOS who are participating in a longitudinal study of in vivo cholesterol metabolism in SLOS, and who have been receiving continuous dietary cholesterol for a median duration of2.9 years. Height, weight, and plasma cholesterol and 7-dehydrocholesterol concentrations were obtained via chart review at three points in time: entry, approximately I year later, and at the last (most recent) assessment. Z scores for height, weight, and weight-for-height were calculated based on age and gender. Plasma concentrations of cholesterol and 7-dehydrocholesterol concentration were measured by gas chromatography. The progress of the group as a whole was analyzed using paired t-tests and linear regression with time of cholesterol concentration.

Results The median z scores for all anthropometric measures were well below average initially (height, weight, and weight-for-height z were -1.73, -2.45, and -1.65, respectively) and throughout follow-up (height, weight, and weight-for-height z were -1.87, -1.89, and -1 .28, respectively). Growth measures did not improve significantly from the time of entry to the last assessment. 71% of patients met the criteria for growth failure, defined as an initial weight for age Z score of -2 or more below the mean at the time of study entry. The most severe growth restriction, in height and weight, occurred in patients fed by G-tube. Initial growth failure and age at initiation of cholesterol did not predict growth outcome. Baseline cholesterol and 7- dehydrocholesterol concentrations did not predict the degree of initial growth restriction when looking at all patients (NS); however, in the subset of patients older than 3 years at study entry, entry weight z score positively correlated (p = 0.030) with baseline plasma cholesterol concentration. In G-tube-fed patients, final cholesterol concentration inversely correlated with final weight-for-height z score (p=0.011). From entry to the first year assessment, a decrease in 7DHC correlated with an increase in annual rate-of-change in height in all patients (p=0.02), as well as in the orally-fed subset (p=0.004), and in the young subset (p=0.02).

Conclusion: These results suggest that growth is restricted in SLOS, most severely in those fed by gastric tube. The degree of growth restriction does not appear to change significantly over time while receiving continuous cholesterol supplementation.

Comments

The digital version of this project is currently unavailable to off-campus users; however, it may be requested via interlibrary loan by eligible borrowers from Pacific University Library. Pacific University Library is a free lender. (Library Use: NL)

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