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Test ID: CTXWB Cerebrotendinous Xanthomatosis, Blood


Ordering Guidance


For assessment of bile acid malabsorption in patients with irritable bowel syndrome-diarrhea, order 7AC4 / 7AC4, Bile Acid Synthesis, Serum.

 

This test is also available as a part of a panel; see HSMWB / Hepatosplenomegaly Panel, Blood. If this test (CTXWB) is ordered with either GPSYW / Glucopsychosine, Blood or OXYWB / Oxysterols, Blood, the individual tests will be canceled and HSMWB ordered.



Specimen Required


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. Do not aliquot.


Forms

1. Biochemical Genetics Patient Information (T602)

2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Useful For

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

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Cerebrotendinous Xanthomatosis, B

Specimen Type

Whole blood

Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole blood Refrigerated (preferred) 72 hours
  Ambient  48 hours

Clinical Information

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. However, more recently, cholic acid has been proposed as an alternative treatment for adults with CTX. Supplementation with beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) inhibitors and coenzyme Q10 has also 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 (eg, 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 CHLGP / Cholestasis Gene Panel, Varies; or order CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies and indicate the gene to be assessed).

Reference Values

7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE (7a-C4)

Cutoff: ≤0.750 nmol/mL

 

7-ALPHA,12-ALPHA-DIHYDROXYCHOLEST-4-en-3-ONE (7a12aC4)

Cutoff: ≤0.250 nmol/mL

Interpretation

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.

Clinical Reference

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, Gallus GN: Cerebrotendinous xanthomatosis. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated March 17, 2022. Accessed December 28, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1409/

5. Lutjohann D, Stellaard F, Bjorkhem I: Levels of 7alpha-hydroxycholesterol and/or 7alpha-hydroxy-4-cholest-3-one are the optimal biochemical markers for the evaluation of treatment of cerebrotendinous xanthomatosis. J Neurol. 2020 Feb;267(2):572-573. doi: 10.1007/s00415-019-09650-0

6. Mandia D, Chaussenot A, Besson G, et al: Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults. J Neurol. 2019 Aug;266(8):2043-2050. doi: 10.1007/s00415-019-09377-y

Day(s) Performed

Tuesday

Report Available

3 to 9 days

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 US Food and Drug Administration.

CPT Code Information

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CTXWB Cerebrotendinous Xanthomatosis, B 92737-6

 

Result ID Test Result Name Result LOINC Value
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
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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