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Test ID CTXBS Cerebrotendinous Xanthomatosis, Blood Spot

Advisory Information

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

Specimen Required


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

Card-Postmortem Screening (Filter Paper) (T525)

Blood Spot Collection Card-Spanish Instructions (T777)

Blood Spot Collection Card-Chinese Instructions (T800)


Preferred: Blood Spot Collection (Filter Paper)

Acceptable: Ahlstrom 226 filter paper, Munktell filter paper, or Postmortem Screening Card

Specimen Volume: 2 blood spots

Collection Instructions:

1. Let blood dry on filter paper at room temperature in a horizontal position for 3 or more 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.

6. Dried blood spots collected with EDTA, sodium heparin, lithium heparin, or ACD B-containing devices are acceptable.

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions in Special Instructions.

Secondary ID


Useful For

Evaluating patients with a clinical suspicion of cerebrotendinous xanthomatosis (CTX)


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

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Refrigerated (preferred) 10 days
  Frozen  59 days
  Ambient  10 days

Reject Due To








Blood spot specimen that shows serum rings, insufficient specimen

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 mutations 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, muscle weakness). Patients may occasionally present with cholestatic liver disease (jaundice, poor growth, 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 HMG-CoA inhibitors and CoQ10 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 MRI (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 diagnosis of CTX can be confirmed by molecular genetic analysis of the CYP27A1 gene (included in: MSNP / Metabolic/Syndromic Neuropathy Panel by Next-Generation Sequencing [NGS]).

Reference Values


Cutoff: ≤0.750 nmol/mL



Cutoff: ≤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 (CTX).


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

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 Jorunal of Rare Diseases 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 GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle. 1993-2019. 2003 Jul 16. Accessed May 2019. Available at

Day(s) and Time(s) Performed

Tuesday and Thursday; 8 a.m.

Analytic Time

2 days (not reported on Saturday or Sunday)

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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


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

NY State Approved



Biochemical Genetics Patient Information (T602) in Special Instructions.