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Test ID: CTXBS Cerebrotendinous Xanthomatosis, Blood Spot


Ordering Guidance


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



Specimen Required


Supplies:

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

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

Container/Tube:

Preferred: Blood Spot Collection (Filter Paper)

Acceptable: Ahlstrom 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 in Special Instructions.

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

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


Useful For

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

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

Reporting Name

Cerebrotendinous Xanthomatosis, BS

Specimen Type

Whole blood

Specimen Minimum Volume

1 Blood spot

Specimen Stability Information

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

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 chenodeoxycholic acid (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).

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 (CTX).

Clinical Reference

1. Mignarri A, Magni A, Del Puppo M, et al: Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2016:39:75-83

2. Nie S, Guiqin C, Xuebing C, 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. 2014:55:146-154

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/

Day(s) Performed

Tuesday

Report Available

2 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
CTXBS Cerebrotendinous Xanthomatosis, BS 92739-2

 

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

mml-biochemical