An Overview of Cerebrotendinous Xanthomatosis (CTX)

Cicely took Brenna, her 11-year-old daughter, to the eye doctor after the youngster's grades began to slip significantly. Since he hadn't noted any problems in prior exams, he was shocked to find that Brenna had cataracts. Only after surgery to remove them did a physician diagnose her with cerebrotendinous xanthomatosis, or CTX.

What is CTX?

This condition is a lipid (fat) storage disorder that can affect multiple areas of the body. According to Genetics Home Reference, afflicted individuals are unable to break down certain forms of cholesterol. As a result, these fats begin to accumulate in various parts of the body.

The word xanthomatosis refers to the production of fatty yellow nodules known as xanthomas. Cerebrotendinous is a reference to the most common locations of xanthomas, the brain (cerebro-) and tendons, structures that attach muscles to bones (-tendinous) .

CTX is a relatively rare condition. Estimates point to 3 to 5 cases per 100,000 people across the globe. However, in the Moroccan Jewish population, the incidence jumps to 1 in 108. Experts believe that the disorder has been seriously underdiagnosed in the United States, according to emedicine. The condition doesn't appear to be more prevalent in either males or females.

Causes

Cerebrotendinous xanthomatosis is caused by a genetic disorder involving mutations in the CYP27A1 gene. This gene normally produces an enzyme essential to breaking down cholesterol. To date, more than 50 mutations have been implicated in the disorder.

Because of gene mutations, the body is unable to break down cholesterol to a specific bile acid known as chenodeoxycholic acid (CDCA). A molecule called cholestanol, similar to cholesterol, starts to accumulate in xanthomas, blood, nerve cells and the patient's brain. Cholesterol levels remain elevated in various tissues. The accumulation of cholesterol and cholestanol in the brain, tendons and other tissues results in the symptoms of CTX.

This condition is the result of an autosomal recessive pattern. This means both copies of the gene in each cell of the body carry mutations. The patient's parents each carry a copy of the damaged gene, though they usually don't show any signs of CTX themselves.

Signs and Symptoms

Although the typical course of this disease starts in infancy with chronic diarrhea, doctors see very few xanthomas in patients younger than 20. Cataracts typically develop in late childhood.

Sometimes the first symptom patients or their families notice is what looks like a lump somewhere on the body. A common xanthoma occurs in the Achilles tendon. These bulges can be both unsightly and painful when they occur in areas such as the elbow or foot. Some patients' bones become progressively brittle and are prone to breaking.

Certain neurological problems in adulthood are also products of cerebrotendinous xanthomatosis. Among them are seizures, dementia, hallucinations, depression, speech problems and difficulty coordinating movements. Experts believe their cause is degeneration of brain tissues linked to excess lipid deposits.

CTX patients also face an elevated risk of developing cardiovascular disease, early-onset Parkinson's disease, gallstones and osteoporosis.

Treatment

If this disorder remains untreated, significant neurological impairment occurs while the patient is in his or her 20s and progresses until death, frequently between 50 and 60. However, the symptoms and course of the disorder vary widely from one patient to another.

In 1971, researchers discovered that CDCA, an important bile acid, was absent in patients with signs of CTX. Unfortunately, treatment can't help all individuals diagnosed with this condition.

The United Leukodystrophy Foundation reports that if cerebrotendinous xanthomatosis is diagnosed before too much deterioration in the patient's brain, treatment can potentially prevent the neurological impairment that results in severe mental dysfunction and subsequent death. Treatment with a CDCA module can stop or slow down the course of CTX. In some cases, it has actually reversed the course of the illness.

Sources:

http://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis

http://emedicine.medscape.com/article/1418820-overview

http://www.ulf.org/types/CTX.html