Xanthomatosis cerebrotendinous, also known as cerebrotendinous xanthomatosis (CTX), is a rare genetic disorder characterized by the accumulation of cholesterol and cholestanol in various tissues of the body, particularly in the brain and tendons. This accumulation leads to the formation of xanthomas, which are fatty deposits that appear as yellowish nodules under the skin and in tendons. CTX is caused by mutations in the CYP27A1 gene, which encodes the enzyme sterol 27-hydroxylase, leading to impaired bile acid synthesis and abnormal cholesterol metabolism.

Symptoms:

1. Neurological Symptoms: Progressive neurological symptoms typically appear in adolescence or early adulthood and may include cognitive impairment, dementia, psychiatric disturbances, ataxia (loss of coordination), spasticity, and seizures.
2. Tendon Xanthomas: Yellowish nodules or swellings that develop in the tendons, particularly in the Achilles tendon, elbows, and knees.
3. Ocular Manifestations: Cataracts and retinal abnormalities may occur.
4. Other Symptoms: Diarrhea, chronic diarrhea, and osteoporosis are also common.

Diagnosis:

• Clinical Evaluation: Based on symptoms such as neurological deficits, tendon xanthomas, and other characteristic features.
• Biochemical Testing: Measurement of serum cholestanol levels, which are elevated in individuals with CTX.
• Genetic Testing: Molecular genetic testing to identify mutations in the CYP27A1 gene.
• Imaging Studies: MRI or CT scans may reveal characteristic changes in the brain associated with CTX.

Treatment:

• Chenodeoxycholic Acid (CDCA) Therapy: Oral supplementation with CDCA, a bile acid precursor, can help normalize bile acid metabolism and reduce the accumulation of cholesterol and cholestanol in tissues.
• Symptomatic Treatment: Management of neurological symptoms, seizures, and other complications as they arise.
• Surgical Intervention: Surgical removal of tendon xanthomas may be considered for cosmetic or functional purposes.

Prognosis:

• Without treatment, CTX is progressive and can lead to severe neurological disability and premature death.
• Early diagnosis and treatment with CDCA can slow or halt disease progression and improve long-term outcomes.
• Lifelong therapy with CDCA is usually required to manage the condition effectively.

Genetic Counseling:

Genetic counseling is recommended for individuals with CTX and their families to understand the inheritance pattern of the condition and the risk of passing the mutated gene to future generations.

Research and Support:

• Ongoing research is focused on developing new treatments and improving the understanding of CTX.
• Support groups and patient organizations may provide valuable resources and support for individuals and families affected by CTX.