Evaluating patients with a clinical suspicion of cerebrotendinous xanthomatosis (CTX)
Monitoring of individuals with CTX on chenodeoxycholic acid (CDCA) therapy
This test is not useful for the identification of carriers
This test is not useful for the evaluation of bile acid malabsorption
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Cerebral cholesterinosis
Cerebrotendinous cholesterosis
Van Bogaert-Scherer-Epstein syndrome
Sterol 27-hydrolase deficiency
Ketosterols
7a-hydroxy-4-cholesten-3-one
7aC4
7a,12a-dihydroxycholest-4-en-3-one
12aC4
7a12aC4
7,12aC4
Whole blood
For assessment of bile acid malabsorption in patients with irritable bowel syndrome-diarrhea, order 7AC4 / 7AC4, Bile Acid Synthesis, Serum.
This test is available separately as well as a part of HSMWB / Hepatosplenomegaly Panel, Blood. If this test is ordered with either GPSYW / Glucopsychosine, Blood or OXYWB / Oxysterols, Blood, the individual tests will be canceled and HSMWB ordered.
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Green top (sodium heparin, lithium heparin), yellow top (ACD B)
Specimen Volume: 1 Ml
Collection Instructions: Send whole blood in original vial.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
0.25 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole blood | Refrigerated (preferred) | 72 hours | |
Ambient | 48 hours |
Evaluating patients with a clinical suspicion of cerebrotendinous xanthomatosis (CTX)
Monitoring of individuals with CTX on chenodeoxycholic acid (CDCA) therapy
This test is not useful for the identification of carriers
This test is not useful for the evaluation of bile acid malabsorption
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis resulting from the deficiency of the mitochondrial enzyme, sterol 27-hydrolase. Sterol 27-hydrolase facilitates the first step of sterol degradation in the formation of bile acids; consequently patients with CTX will experience increased storage of the sterol, cholestenol, and ketosterol bile acid precursors (7-alpha-hydroxy-4-cholesten-3-one [7a-C4] and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one [7a12aC4]) in multiple tissues throughout the body with a resulting deficiency of the bile acid, chenodeoxycholic acid (CDCA). CTX is caused by variants in the CYP27A1 gene.
Patients with CTX can present with a constellation of findings including infantile onset diarrhea, childhood onset cataracts, development of tendon/cerebral xanthomas in adolescence and early adulthood, early onset osteoporosis, as well as a broad array of neuropsychological manifestations such as intellectual disability, dementia, psychiatric symptoms, ataxia, pyramidal signs, dystonia, and muscle weakness. Patients may occasionally present with cholestatic liver disease, which may present as jaundice, poor growth, and hepatosplenomegaly. Intrafamilial variability exists, and some heterozygous carriers may experience a higher incidence of cardiac disorders or gallstones. Treatment with CDCA normalizes bile acid synthesis and suppresses cholestenol biosynthesis, with improvement of clinical symptoms and arrest of disease progression. Supplementation with beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) inhibitors and coenzyme Q10 has been proposed. The availability of effective therapy makes early diagnosis and treatment of patients with CTX essential.
The estimated incidence of CTX is 1 in 50,000 individuals of Northern European ancestry and as high as 1 in 440 in the Druze population of Israel.
The diagnostic evaluation of patients with suspected CTX may reveal abnormalities on brain magnetic resonance imaging (such as cerebellar atrophy, decrease in volume of grey and white matter, and abnormal white matter signal) in addition to the biochemical and clinical abnormalities. The biochemical diagnosis of CTX can be confirmed by molecular genetic analysis of the CYP27A1 gene (included in: NPPAN / Peripheral Neuropathy Genetic Panels by Next-Generation Sequencing [NGS], Blood).
7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE (7a-C4)
Cutoff: < or =0.750 nmol/mL
7-ALPHA,12-ALPHA-DIHYDROXYCHOLEST-4-en-3-ONE (7a12aC4)
Cutoff: < or =0.250 nmol/mL
An elevation of 7-alpha-hydroxy-4-cholesten-3-one (7a-C4) and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4) is strongly suggestive of cerebrotendinous xanthomatosis.
Patients with bile acid malabsorption or ileal resection may have elevations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4).
1. Mignarri A, Magni A, Del Puppo M, et al: Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2016 Jan:39(1):75-83
2. Nie S, Chen G, Cao X, Zhang Y: Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2014 Nov 26;9:179
3. DeBarber AE, Luo J, Star-Weinstock M, et al: A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J. Lipid Res. 2014 Jan:55(1):146-154
4. Federico A, Dotti MT, Gallus GN: Cerebrotendinous xanthomatosis. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated April 14, 2016. Accessed November 20, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1409/
Whole blood is spotted on filter paper and dried overnight. A 3-mm dried blood spot is extracted with internal standard. The extract is subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS/MS is operated in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for each analyte and internal standard. The ratio of the extracted peak areas to internal standard is determined by LC-MS/MS is used to calculate the concentration of in the sample.(Unpublished Mayo method)
Tuesday
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 US Food and Drug Administration.
82542
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CTXWB | Cerebrotendinous Xanthomatosis, B | 92737-6 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
BA4365 | Interpretation (CTXWB) | 59462-2 |
BA4363 | 7a-hydroxy-4-cholesten-3-one | 92762-4 |
BA4364 | 7a,12a-dihydroxycholest-4-en-3-one | 92759-0 |
BA4366 | Reviewed By | 18771-6 |