Test Catalog

Test Id : CTXBS

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Cerebrotendinous Xanthomatosis, Blood Spot

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluating patients with a clinical suspicion of cerebrotendinous xanthomatosis (CTX) using dried blood spot specimens

 

Monitoring 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
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Cerebrotendinous Xanthomatosis, BS

Aliases
Lists additional common names for a test, as an aid in searching

Cerebral cholesterinosis

Cerebrotendinous cholesterosis

Van Bogaert-Scherer-Epstein syndrome

Sterol 27-hydrolase deficiency

Ketosterols

7a-hydroxy-4-cholesten-3-one

7aC4

7-a,12 a-dihydroxycholest-4-en-3-one

12aC4

7a12aC4

7,12aC4

CTX

Specimen Type
Describes the specimen type validated for testing

Whole 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 HSMBS / Hepatosplenomegaly Panel, Blood Spot. If this test (CTXBS) is ordered with either GPSY / Glucopsychosine, Blood Spot or OXYBS / Oxysterols, Blood Spot, the individual tests will be canceled and HSMBS ordered.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies:

-Card-Blood Spot Collection (Filter Paper) (T493)

-Card-Postmortem Screening (Filter Paper) (T525)

Container/Tube:

Preferred: Blood Spot Collection Card (Filter Paper)

Acceptable: Whatman Protein Saver 903 filter paper, PerkinElmer 226 filter paper, Munktell filter paper, Postmortem Screening Card or collected with EDTA, sodium heparin, lithium heparin, or ACD B-containing devices

Specimen Volume: 2 Blood spots

Collection Instructions:

1. Let blood dry completely on filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

2. At least 1 spot should be complete (ie, unpunched).

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

1 Blood spot

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Blood spot showing serum rings
Insufficient specimen
Layering
Multiple applications 		Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole blood Refrigerated (preferred) 10 days FILTER PAPER
Frozen 59 days FILTER PAPER
Ambient 10 days FILTER PAPER

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluating patients with a clinical suspicion of cerebrotendinous xanthomatosis (CTX) using dried blood spot specimens

 

Monitoring 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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 is an important enzyme in both the alternative and classic bile acid synthesis pathways. 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 disease-causing 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 can be substantial. Some heterozygous carriers may experience a higher incidence of cardiac disorders or gallstones; however, carriers are typically asymptomatic. Treatment with CDCA has been shown to improve both biochemical and clinical outcomes in patients with CTX. Supplementation with beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) reductase inhibitors can be used as alternative treatment alone or in combination with CDCA. Cholic acid treatment has been used in few patients showing a decrease in cholestanol levels and improvement in neurologic symptoms. The availability of effective therapy makes early diagnosis and treatment of patients with CTX essential.

 

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
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.

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

Interpretation
Provides information to assist in interpretation of the test results

An elevation of 7-alpha-hydroxy-4-cholesten-3-one (7aC4) or 7-alpha,12 alpha-dihydroxycholest-4-en-3-one (7a12aC4) or both is strongly suggestive of cerebrotendinous xanthomatosis.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Patients with bile acid malabsorption or ileal resection may have elevations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Mignarri A, Magni A, Del Puppo M, et al. Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2016;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;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;55(1):146-154

4. Federico A, Gallus GN. Cerebrotendinous xanthomatosis. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet].University of Washington, Seattle; 2003. Updated November 14, 2024. Accessed November 29, 2024. 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;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;266(8):2043-2050. doi:10.1007/s00415-019-09377-y

7. Nobrega PR, Bernardes AM, Ribeiro RM, et al. Cerebrotendinous xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment. Front Neurol. 2022;13:1049850. Published 2022 Dec 23. doi:10.3389/fneur.2022.1049850

Method Description
Describes how the test is performed and provides a method-specific reference

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 determined by the LC-MS/MS is used to calculate the concentration of in the sample.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Tuesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 9 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Normal: 2 months; Abnormal: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82542

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CTXBS Cerebrotendinous Xanthomatosis, BS 92739-2
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.
BA4361 Interpretation (CTXBS) 59462-2
BA4359 7a-hydroxy-4-cholesten-3-one 92763-2
BA4360 7a,12a-dihydroxycholest-4-en-3-one 92760-8
BA4362 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports