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Test Catalog

Test ID: CTXWB    
Cerebrotendinous Xanthomatosis, Blood

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

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

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 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).

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 (7a-C4) and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4) 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. 2016:39:75-83

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. 2014:55:146-154

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/