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A genetic variant in a cholesterol-processing enzyme that, when inherited from both parents, causes a treatable but often overlooked disorder of fat and cholesterol buildup throughout the body.
This test looks at a specific spot in your DNA, the CYP27A1 gene, to determine whether you carry a change that impairs your body's ability to process cholesterol into bile acids. The variant is called CYP27A1 c.1435C>T (p.Arg479Cys), and it swaps one amino acid for another in an enzyme called sterol 27-hydroxylase. What matters to you is not the molecular detail but the practical consequence: if you carry two copies of this (or a similar) change, your body cannot properly complete a key step in cholesterol metabolism, and a treatable condition called cerebrotendinous xanthomatosis (CTX) can develop. If you carry one copy, you are a carrier, generally healthy, but with information that matters for family planning and possibly for cardiovascular risk.
CTX is rare, inherited in an autosomal recessive pattern, meaning you need a faulty copy from each parent. It is also dramatically underdiagnosed. The average age at diagnosis is 35 years, with a delay of 16 to 25 years from when symptoms first appear. That delay matters because early treatment can prevent irreversible damage, while late treatment may only slow progression.
Your liver converts cholesterol into bile acids, which help you digest fats and regulate cholesterol levels. Sterol 27-hydroxylase is one of the key enzymes in that conversion. The Arg479Cys change sits right next to the enzyme's heme-binding site, the part of the protein that makes it catalytically active. When both copies of the gene carry damaging variants, the enzyme essentially stops working.
Without functional sterol 27-hydroxylase, your body cannot produce enough of a bile acid called chenodeoxycholic acid. Instead, cholesterol gets shunted into an alternative pathway that produces cholestanol, a related molecule that accumulates in your blood, brain, tendons, eyes, and other tissues. About 41% of all CTX-causing mutations occur in the regions of the gene (exons 6 through 8) that encode the enzyme's most functionally critical domains.
Your result will show one of three possibilities, depending on how many copies of the variant you carry.
If both you and your partner are carriers, each child has a 25% chance of inheriting two faulty copies and developing CTX. This is why carrier status has direct implications for reproductive planning.
CTX is a progressive, multisystem condition, but its earliest signs often appear in childhood, well before anyone suspects a genetic disorder. Knowing what to look for can close that 16-to-25-year diagnostic gap.
The earliest symptom is often chronic diarrhea beginning in infancy. Some newborns also develop prolonged jaundice (cholestasis). Cataracts that appear in childhood or adolescence are another hallmark, present in 76% to 88% of people with CTX. These cataracts have a characteristic pattern of diffuse flecks with opacities at the back of the lens.
Later, the disease can produce tendon xanthomas (fatty deposits, especially in the Achilles tendons), progressive neurological problems including difficulty with balance and coordination (ataxia), leg stiffness (spastic paraparesis), cognitive decline, seizures, peripheral nerve damage, and psychiatric symptoms. Premature atherosclerosis and osteoporosis also occur.
If you carry two copies and have any of these features, the combination of elevated blood cholestanol and elevated urinary bile alcohols can confirm the diagnosis biochemically.
Because this is a genetic variant, nothing changes the genotype itself. But if you or a family member has CTX, the downstream biochemical abnormalities (high cholestanol, low chenodeoxycholic acid) respond to treatment, and timing is everything.
Chenodeoxycholic acid (CDCA) is the primary treatment. It replaces the bile acid your body cannot make, which in turn suppresses the buildup of cholestanol. The standard dose is 750 mg per day in adults and 10 to 20 mg per kg per day in children. In a randomized, placebo-controlled crossover trial, CDCA normalized plasma and cerebrospinal fluid cholestanol levels and stabilized or improved nerve function, pyramidal symptoms, and cerebellar symptoms.
The window for treatment matters enormously. In a nationwide study, every person diagnosed before age 28 showed either neurological stabilization or improvement with CDCA (100%). Treatment started within 15 years of neurological symptom onset led to significant clinical improvement. But when treatment began more than 25 years after neurological symptoms appeared, it could only slow further decline. Most powerfully, children treated before symptoms develop can be completely spared the CTX phenotype.
What this means for you: if your genetic result shows two pathogenic copies and you have not yet been evaluated, seek treatment promptly. Even a few years of delay can mean the difference between reversible and irreversible neurological damage. If your child is a known carrier and your partner is also a carrier, testing your child early can enable treatment before any damage occurs.
Cholic acid is an FDA-approved alternative for those who cannot tolerate CDCA.