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Test ID: SLO Smith-Lemli-Opitz Screen, Plasma

Reporting Name

Smith-Lemli-Opitz Scrn, P

Useful For

Diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency)

Clinical Information

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 important roles 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. Disorders that result from a deficiency of these enzymes lead to an accumulation of specific intermediates and inhibit the formation of important biomolecules. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.

 

Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder caused by variants in the DHCR7 gene leading to a deficiency of the 7-dehydrocholesterol reductase enzyme. It is characterized biochemically by markedly increased plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) levels. Clinically, 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. However, the clinical spectrum ranges from mild to severe with some mildly affected individuals presenting with only 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 underdiagnoses 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).

Interpretation

Elevated plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (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 some antipsychotic or antidepressant medications including haloperidol, aripiprazole, and trazodone. However, the 7-DHC to cholesterol ratio is typically elevated only in SLO patients.

Report Available

3 to 9 days

Day(s) Performed

Tuesday, Friday

Clinical Reference

1. Donoghue SE, Pitt JJ, Boneh A, White SM: Smith-Lemli-Opitz syndrome: clinical and biochemical correlates. J Pediatr Endocrinol Metab. 2018;31(4):451-459

2. Nowaczyk MJM: Smith-Lemli-Opitz syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; November 13, 1998. Updated January 30, 2020. Accessed July 20, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1143/

3. Hall P, Michels V, Gavrilov D, et al: Aripiprazole and trazodone cause elevations of 7-dehydrocholesterol in the absence of Smith-Lemli-Opitz syndrome. Mol Genet Metab. 2013 Sep-Oct;110(1-2):176-178

4. Genaro-Mattos TC, Tallman KA, Allen LB, et al: Dichlorophenyl piperazines, including a recently-approved atypical antipsychotic, are potent inhibitors of DHCR7, the last enzyme in cholesterol biosynthesis. Toxicol Appl Pharmacol. 2018 Jun 15;349:21-28. doi: 10.1016/j.taap.2018.04.029

Method Name

Gas Chromatography-Mass Spectrometry (GC-MS)

Specimen Type

Plasma


Specimen Required


Collection Container/Tube:

Preferred: Green top (sodium or lithium heparin)

Acceptable: Lavender top (EDTA), pearl white top (EDTA plasma gel), yellow top (ACD A/ACD B)

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions:

1. Centrifuge and aliquot plasma into plastic vial.

2. Send plasma frozen.


Specimen Minimum Volume

0.1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma Frozen (preferred) 92 days
  Refrigerated  28 days
  Ambient  14 days

Reference Values

7-DEHYDROCHOLESTEROL

≤2.0 mg/L

 

8-DEHYDROCHOLESTEROL

≤ 0.3 mg/L

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SLO Smith-Lemli-Opitz Scrn, P 73852-6

 

Result ID Test Result Name Result LOINC Value
29972 Interpretation 59462-2
610625 7-Dehydrocholesterol 33275-9
610626 8-Dehydrocholesterol 34671-8
29974 Reviewed By 18771-6

Forms

If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen. 

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Pediatric, mml-Neurometabolic