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How to recognize the signs and symptoms of CTX

It is important to understand that the signs and symptoms of CTX vary from patient to patient, and neurological symptoms can worsen over time.

Hallmark Manifestations

  • Chronic diarrhea beginning during infancy is a hallmark symptom.
  • Cataracts in both eyes commonly appear in children and adolescents, although they may not develop at the same time and may occur later in life.
  • Xanthomas, or fatty, yellow deposits in the tendons and other organs, may develop in adolescents and young adults, and most commonly on the knees, Achilles tendons, and elbows.
  • Severe neurological signs of the disease (seizures, dementia, movement disorders) usually become apparent in young adulthood. However, in some cases, neurological symptoms such as decreased muscle coordination, abnormal reflexes, and intellectual decline can occur as early as adolescence, and cognitive impairment, developmental delays, and epilepsy may appear during childhood.1,2

If CTX is untreated, patients are likely to die between the 4th and 6th decades of life.3

What to Look For

Hear more from CTX experts.


Xanthomas, fatty, yellow deposits which most often appear on the Achilles tendon, are a common symptom in adolescents and adults with CTX.1 Photo courtesy of William Connor, MD, Oregon Health and Science University.3

Symptoms of CTX in Infants and Young Children4,5

Main symptoms:

  • Chronic diarrhea
  • Bilateral cataracts

Other symptoms:

  • Long-lasting jaundice in newborns
  • Developmental delays and neurological issues such as abnormal behavior and learning disability
  • Eye problems such as blurred vision, blind spots, or vision loss
  • Autism spectrum disorder
  • Epilepsy

Symptoms of CTX in Adolescents and Adults4

Main Symptoms

  • Neurological problems including learning disabilities, seizures, dementia, and Parkinson-like tremors
  • Xanthomas
  • Psychiatric symptoms including behavioral changes, hallucinations, agitation, aggression, and depression
  • Increased stiffness, slow movement, abnormal walk

Other Symptoms

  • Atherosclerosis
  • Osteoporosis and bone fractures
  • Other vision problems

Early Diagnosis is Critical!

A review of 55 patients reported a mean age of CTX symptom onset was 9.5±9.0 years old and the mean age of diagnosis was 35.5±11.8 years old, with a substantial diagnostic delay of 20-25 years6. By the time of diagnosis, they may have already begun experiencing neurological and psychiatric problems. Given that the symptoms and progression of CTX can vary widely from person to person, timely diagnosis is critical, as treatment can dramatically alter the course of the disease, especially when started in the disease’s early stages.3

What causes CTX?

CTX occurs when a faulty gene fails to produce a key enzyme.

CYP27A1 Gene

CTX is an autosomal recessive disease, meaning that people affected by the disease are born with two defective copies of the CYP27A1 gene, which normally provides instructions for producing an enzyme called sterol 27-hydroxylase. Individuals born with just one copy of the damaged gene are known as carriers and are generally not affected by CTX. The sterol 27-hydroxylase enzyme works in the liver to break down cholesterol to form the primary bile acids chenodeoxycholic acid (CDCA) and cholic acid (CA).7

Mutations in the CYP27A1 gene cause the sterol 27-hydroxylase enzyme to malfunction and interfere with the formation of primary bile acids. The disruption of these metabolic pathways also leads to the formation and accumulation of cholestanol (a lipid similar to cholesterol) and abnormal bile alcohols in various tissues in the body over time, producing the symptoms of CTX.8

Concerns About CTX?

If you are suspicious of or diagnosed with CTX, please seek your local healthcare practitioners for professional consultation, as practice and referral systems vary from country to country.


  1. Federico A, Dotti MT, Gallus GN. Cerebrotendinous xanthomatosis. In: Adam MP, Ardinger HH, Pagon RA et al, editors. Gene Reviews [Internet]. Seattle: University of Washington; 2013; updated 2016. Accessed 25 January 2018.
  2. Verrips A. Cerebrotendinous xenthomatosis. In: Hollak CEM, Lachmann R. eds. Inherited Metabolic Disease in Adults: A Clinical Guide. Oxford University Press; 2016: Ch. 40.
  3. Steiner RD. Cerebrotendinous xanthomatosis. Medscape; 2015; updated 2017. Accessed 29 January 2018.
  4. Berginer VM, Gross B, Morad K, Kfir N. Chronic diarrhoea and juvenile cataracts: Think Cerebrotendinous Xanthomatosis and treat. Pediatrics. 2009;123:143-7.
  5. Stelten BML, Bonnot O, Huidekoper HH, et al. Autism spectrum disorder: an early and frequent feature in cerebrotendinous xanthomatosis. Journal of Inherited Metabolic Disease. 2017. doi: 10.1007/s10545-017-0086-7. [Epub ahead of print]
  6. Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. Journal of Inherited Metabolic Disease. 2014;37:421-9.
  7. Verrips A, Cruysberg JRM, Wevers RA. Cerebrotendinous xanthomatosis. In: Roach ES, Miller VS, eds. Neurocutaneous Disorders. Cambridge University Press; 2004. Ch. 30.
  8. Moghadasian M. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clinical and Investigative Medicine.2004;27(1):42-50.
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