Smith-Lemli-Opitz Screen, Plasma
Diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency)
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Cholesterol plays an essential role in many cellular and developmental processes. In addition to its role as a membrane lipid, it is the precursor to numerous molecules that play an important role in cell growth and differentiation, protein glycosylation, and signaling pathways. The biosynthesis of cholesterol and its subsequent conversion to other essential compounds is complex, involving a number of intermediates and enzymes. In addition to an accumulation of specific intermediates, defects in this pathway may result in a deficiency of cholesterol. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the DHCR7 gene leading to a deficiency of the 7-dehydrocholesterol reductase enzyme. It is characterized by markedly increased plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-DHC levels. Clinical features can include microcephaly, growth retardation, developmental delay, dysmorphic facial features, cleft palate, limb abnormalities (especially 2-3 syndactyly of the toes and postaxial polydactyly), and heart and kidney malformations. Severity of SLOS ranges from severe to mild. Some mildly affected individuals may only have 2 to 3 toe syndactyly and mild cognitive impairment. The reported incidence is between 1 in 10,000 and 1 in 60,000, but it may be more prevalent due to underdiagnosis of mildly affected individuals.
Other disorders of cholesterol biosynthesis, including desmosterolosis (desmosterol reductase deficiency) and sitosterolemia, may present with similar manifestations. These disorders can be detected biochemically by performing a quantitative profile of plasma sterols (STER / Sterols, Plasma).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Negative (reported as positive or negative)
Quantitative results are provided when positive.
Elevated plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-DHC are highly suggestive of a biochemical diagnosis of Smith-Lemli-Opitz (SLO).
Mild elevations of these cholesterol precursors can be detected in patients with hypercholesterolemia and patients treated with haloperidol. However, the 7-DHC to cholesterol ratio is only elevated in SLO patients.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The enzymatic tests for measuring plasma cholesterol quantitate all 3 hydroxysterols and are unreliable for diagnosis for Smith-Lemli-Opitz.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Haas D, Kelley RI, Hoffmann GF: Defects of cholesterol biosynthesis. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou. New York, McGraw-Hill Medical, 2009, pp 313-321
2. Irons M: Smith-Lemli-Opitz Syndrome. 1998 Nov 13 9 Updated 2007 Oct 240. In GeneReviews [Internet]. Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle, 1993. Available from URL: http://www.ncbi.nlm.nih.gov/books/NBK1143/