Sterol 27-Hydroxylase Deficiency

Sterol 27-hydroxylase deficiency is a rare genetic disease where a gene called CYP27A1 does not work properly. This gene makes an enzyme that helps turn cholesterol into normal bile acids. When the enzyme is missing, abnormal fats such as cholestanol build up in the brain, eyes, tendons, and other organs. This condition is also called cerebrotendinous xanthomatosis (CTX). It can cause long-term diarrhea in babies, early cataracts in children, tendon lumps (xanthomas) in teenagers, and slowly worsening brain and nerve problems in adults if it is not treated early.NCBI+1

Sterol 27-hydroxylase deficiency is a rare genetic disease where the body cannot properly turn cholesterol into some important bile acids, because an enzyme called sterol 27-hydroxylase does not work well or is missing. This problem makes abnormal fats, especially a substance called cholestanol, build up slowly in the brain, eyes, tendons, bones, and other organs, and this can cause many body and nerve problems over time. PubMed+2PMC+2

Sterol 27-hydroxylase deficiency is caused by harmful changes (mutations) in a gene called CYP27A1. This gene gives the body the “recipe” to make the sterol 27-hydroxylase enzyme, which normally sits in the mitochondria (the energy centers of the cell) and helps break down cholesterol into bile acids that help digest fats. When this gene is damaged, the pathway is blocked and toxic sterol by-products build up. MedlinePlus+2Abdominal Key+2

The main evidence-based treatment is bile acid replacement, especially chenodeoxycholic acid (CDCA). Giving the missing bile acid lowers cholestanol levels, protects the brain, and can stop or slow the disease, especially if treatment starts early in life. Other medicines, surgeries, diet changes, and rehabilitation are usually added to manage symptoms and complications.PMC+2Frontiers+2

Because cholestanol and related sterols collect slowly in tissues, symptoms often start in childhood or young adulthood and then get worse if the disease is not treated. People can have long-lasting diarrhea, early cataracts, tendon lumps called xanthomas, walking and balance problems, learning and memory problems, mental health changes, weak bones, and early heart disease. PMC+2Orpha+2

Other names

Sterol 27-hydroxylase deficiency is most widely known as cerebrotendinous xanthomatosis (CTX). The name “cerebro-” refers to the brain, “tendinous” refers to tendons, and “xanthomatosis” refers to the yellow fatty lumps (xanthomas) that form in these places. PMC+2Orpha+2

Another older name is “cerebral cholesterosis”, which means abnormally high cholesterol-like material in the brain, because doctors first noticed fat deposits and damage in the nervous system. Wikipedia+1

It is also called “CYP27A1 deficiency” or “CYP27A1-related cerebrotendinous xanthomatosis,” to show that the disease comes from harmful variants in the CYP27A1 gene that encodes the sterol 27-hydroxylase enzyme. Mayo Clinic Laboratories+1

Some older papers use the name “Van Bogaert–Scherer–Epstein syndrome” for the same condition, based on the names of early doctors who described the disease. Wikipedia+1

Types

Doctors usually describe three main clinical forms (patterns) of sterol 27-hydroxylase deficiency. These forms overlap, and one patient can show features from more than one group, but the names help organize how the disease looks in real life. PMC+2J-STAGE+2

1. Classic (generalized) CTX form – In this common form, people have early diarrhea and cataracts, later tendon xanthomas, and progressive brain and nerve problems like ataxia (unsteady walk), stiffness, weakness, and cognitive decline. Orpha+2J-STAGE+2

2. Spinal form – In the spinal form, the main problem is long-lasting damage in the spinal cord (chronic myelopathy), causing stiff legs, spastic paraplegia, and walking difficulty, often with few or no tendon xanthomas and sometimes milder other symptoms. J-STAGE+2ResearchGate+2

3. Non-neurological form – In this form, there may be cataracts, diarrhea, xanthomas, or osteoporosis, but brain and spinal symptoms are mild or appear very late, so the disease may be missed for many years. PMC+2Medlink+2

4. Infantile liver-predominant presentation – Some babies mainly show prolonged jaundice or cholestasis (poor bile flow) and liver disease, before eye, tendon, or brain signs are obvious, which can lead to misdiagnosis as a simple liver problem. Abdominal Key+2Ethernet University+2

5. Asymptomatic or very mild form – A few people with CYP27A1 mutations are found only by family screening or blood tests; they may have high cholestanol but almost no clear symptoms yet, which makes early detection very important. PMC+2Wiley Online Library+2

Causes

Medically, there is one direct cause of sterol 27-hydroxylase deficiency: harmful mutations in both copies of the CYP27A1 gene. The 20 points below describe different genetic patterns and biological mechanisms that explain how this single cause works and why the disease develops and progresses. MedlinePlus+2Mayo Clinic Laboratories+2

1. Autosomal recessive inheritance – The disease appears when a person inherits one faulty CYP27A1 gene from each parent, so the child has two changed copies and very low enzyme activity, while each parent is usually a healthy carrier. Orpha+1

2. Homozygous missense mutations – Some patients have the same missense mutation in both gene copies, causing a small change in the enzyme’s structure that makes it work poorly, so cholesterol is not processed into bile acids correctly. Cell+1

3. Compound heterozygous mutations – Other patients carry two different CYP27A1 mutations, one from each parent, such as one missense and one frameshift change, which together severely reduce enzyme function and lead to CTX. Springer Link+1

4. Nonsense and frameshift mutations – Some mutations create a “stop” signal or shift the reading frame, making a very short, non-functional enzyme that cannot perform the necessary bile acid synthesis steps. Cell+1

5. Splice-site mutations – Changes at the boundaries between exons and introns can disturb normal RNA splicing, so the final message for the enzyme is faulty, giving very low or absent sterol 27-hydroxylase activity. Wiley Online Library+1

6. Large deletions or insertions in CYP27A1 – In some families, parts of the gene are missing or duplicated, so the enzyme cannot be built correctly and the cholesterol-to-bile-acid pathway is broken. Wiley Online Library+1

7. Defective mitochondrial targeting of the enzyme – Sterol 27-hydroxylase normally lives in the mitochondria; certain mutations disturb how it is transported or anchored there, so even if the enzyme is made, it cannot work in the right place. ScienceDirect+1

8. Loss of chenodeoxycholic and cholic acid production – When sterol 27-hydroxylase is missing, production of bile acids, especially chenodeoxycholic acid (CDCA) and cholic acid, drops, removing a normal “feedback brake” on cholesterol breakdown and disturbing fat digestion. Frontiers+2Springer Medizin+2

9. Over-production of bile acid intermediates – Because the feedback brake is gone, another enzyme (cholesterol 7α-hydroxylase) becomes overactive and produces large amounts of intermediates like 7α-hydroxy-4-cholesten-3-one, which are then turned into cholestanol and bile alcohols. PMC+2Wikipedia+2

10. Accumulation of cholestanol in tissues – The abnormal sterol cholestanol builds up in the brain’s white matter, eye lenses, tendons, bones, and vessels, slowly damaging these tissues and causing many of the symptoms of CTX. PubMed+2ResearchGate+2

11. Disrupted reverse cholesterol transport in macrophages – Sterol 27-hydroxylase helps move cholesterol out of cells such as macrophages; when the enzyme is missing, cholesterol handling is abnormal, promoting xanthoma formation and vessel damage. Nanbyo Lipid+1

12. Toxic effects on brain cells – Abnormal sterols collecting in the brain can upset myelin (the covering around nerves), damage neurons, and disturb signaling, leading to movement problems, seizures, and cognitive changes. JBC+2PMC+2

13. Secondary mitochondrial stress – Sterol build-up in mitochondria may disturb energy production and increase oxidative stress in nerve and muscle cells, which adds to weakness and neurologic problems. ScienceDirect+2MDPI+2

14. Changes in bone metabolism – Abnormal bile acid and sterol patterns affect vitamin D and calcium handling, contributing to low bone mineral density and osteoporosis in many patients. Wikipedia+2SciSpace+2

15. Early liver involvement in infancy – In some babies, the enzyme defect first appears as neonatal jaundice or cholestasis, which shows that the liver is already under stress from abnormal bile acid synthesis. Abdominal Key+2Orpha+2

16. Phenotypic variability from different mutations – Different CYP27A1 variants can cause milder or more severe enzyme loss, which partly explains why some people have mainly spinal symptoms, while others have classic multi-system disease. PMC+2Wiley Online Library+2

17. Possible modifying genes or environmental factors – Studies of families with the same mutations but different disease severity suggest that other genes and life factors can change how strongly the enzyme defect shows in the body. Springer Link+2SciSpace+2

18. Consanguinity (parents related by blood) – In some regions, marriage between relatives increases the chance that both parents carry the same rare CYP27A1 mutation, so their children have a higher risk of being affected. SciSpace+2ScienceDirect+2

19. Founder mutations in specific populations – Certain countries or ethnic groups have common recurrent CYP27A1 variants that were passed down from a distant ancestor, which leads to more CTX cases in those communities. Wiley Online Library+2ResearchGate+2

20. Delayed diagnosis and continued sterol build-up – While this does not cause the mutation itself, late diagnosis means the biochemical problem continues unchecked for years, allowing more cholestanol to accumulate and making symptoms more severe and harder to reverse. Frontiers+2DNB Portal+2

Symptoms

1. Chronic diarrhea in infancy or childhood – Many children with this disease have long-lasting, unexplained watery stools, often starting in the first years of life, because abnormal bile acids irritate the gut and disturb fat absorption. PMC+2Orpha+2

2. Neonatal jaundice or cholestasis – Some babies have yellow skin and eyes or poor bile flow soon after birth; this early liver problem is one of the first signs that bile acid production is not normal. Abdominal Key+2Orpha+2

3. Early-onset cataracts – Clouding of the eye lens can appear in childhood or the teenage years, often in both eyes, and can lead to poor vision or need for surgery if not recognized as part of CTX. PMC+2JAMA Network+2

4. Tendon xanthomas – Firm, yellowish lumps form in tendons such as the Achilles or around the knees and elbows; they are made of fat and cholestanol deposits and usually appear in late childhood or early adulthood. ScienceDirect+2IJDVL+2

5. Gait problems and ataxia – Many patients develop unsteady walking, frequent falls, or difficulty with balance and coordination because of damage to the cerebellum and spinal pathways. PMC+2Orpha+2

6. Learning difficulties and cognitive impairment – Children may struggle at school, and adults may have problems with memory, thinking, planning, or understanding, reflecting slow injury to brain networks. Lipid Journal+2SciSpace+2

7. Progressive dementia – Over time, some people develop more serious loss of memory and daily function, with trouble managing personal care or work as the disease advances without treatment. PMC+2IJDVL+2

8. Peripheral neuropathy – Numbness, tingling, burning, or weakness in the feet and hands can occur because abnormal sterols damage peripheral nerves, often adding to walking problems. Bangladesh Journals Online+2Radboud Repository+2

9. Psychiatric and behavioral changes – Depression, anxiety, irritability, personality changes, hallucinations, or other mental health problems can appear, and sometimes these symptoms are the first signs noticed in young adults. Wikipedia+2PMC+2

10. Seizures (epilepsy) – Some patients have epileptic seizures, which happen because of abnormal electrical activity in brain areas damaged by cholestanol deposits and white-matter changes. Wikipedia+2SciSpace+2

11. Parkinsonism and other movement disorders – Slow movement, stiffness, tremor, dystonia (twisting movements), or palatal myoclonus (palate jerks) can occur as the deep brain structures are affected. Wikipedia+2JBC+2

12. Muscle weakness and fatigue – People may feel their muscles tire quickly, especially in the legs, due to a mix of neuropathy, myelopathy, and possible muscle involvement. ScienceDirect+2Radboud Repository+2

13. Osteoporosis and bone fractures – Many adults with CTX have low bone density and may suffer bone fractures after minor falls, likely related to long-term bile acid and vitamin D disturbance. Bangladesh Journals Online+2Wikipedia+2

14. Premature atherosclerosis and heart disease – Even when standard cholesterol levels are not very high, patients can develop early hardening of the arteries and heart problems because of abnormal sterol patterns. Bangladesh Journals Online+2Wikipedia+2

15. Speech and swallowing problems (dysarthria, dysphagia) – As brain and brainstem involvement increases, some patients speak with slurred speech and may choke on food or liquids, showing advanced neurologic disease. Springer Link+2PMC+2

Diagnostic tests

Doctors diagnose sterol 27-hydroxylase deficiency by combining physical and neurological examination, bedside tests, special blood tests, genetic testing, electrical studies, and imaging. Together these tests show the clinical picture, the biochemical pattern of high cholestanol and abnormal bile acids, and the CYP27A1 mutation that confirms CTX. PMC+2Wikipedia+2

Physical exam tests

1. General physical and growth examination – The doctor checks height, weight, body build, and overall health, looking for short stature, thin build from chronic diarrhea, or signs of poor nutrition, as well as jaundice or enlarged liver in infants. Orpha+2ResearchGate+2

2. Neurological examination – The clinician tests strength, muscle tone, reflexes, sensation, and coordination to look for spasticity, weakness, ataxia, sensory loss, and other signs of brain and spinal cord involvement typical of CTX. PMC+2PMC+2

3. Eye examination (including slit-lamp exam) – An ophthalmologist checks visual acuity and examines the lenses with a slit lamp to detect early or advanced cataracts and other lens changes that strongly suggest CTX in young people. JAMA Network+2aboutctxhcp.com+2

4. Musculoskeletal and tendon examination – The doctor carefully feels the Achilles tendons, knees, elbows, and hands for firm, painless lumps (xanthomas) and looks for bone deformities or spine curvature linked to osteoporosis. ScienceDirect+2IJDVL+2

Manual bedside tests

5. Gait and balance tests (including heel-to-toe walking) – The patient is asked to walk normally and in a straight line with one foot in front of the other; difficulty or side-to-side swaying points to cerebellar ataxia or spinal involvement. PMC+2Radboud Repository+2

6. Romberg test – The patient stands with feet together and eyes closed; increased swaying or falling shows problems in the sensory pathways or spinal cord, which are often affected in spinal or classic CTX forms. Radboud Repository+2J-STAGE+2

7. Manual muscle strength testing – The examiner pushes against the patient’s arms and legs in different directions to check power; weakness or rapid fatigue helps document motor involvement from neuropathy or myelopathy. Bangladesh Journals Online+2PMC+2

8. Coordination tests (finger-to-nose, heel-to-shin) – Simple pointing tasks show whether the cerebellum and its connections work properly; overshooting, tremor, or clumsiness support the diagnosis of a cerebellar-type disorder like CTX. PMC+2ScienceDirect+2

Lab and pathological tests

9. Serum cholestanol level – This is a key biochemical marker; CTX patients typically have clearly raised cholestanol levels, much higher than normal, because the enzyme block forces cholesterol into this abnormal product. PubMed+2Mayo Clinic Laboratories+2

10. Plasma bile alcohols and bile acid intermediates – Special tests can measure unusual bile alcohols and intermediates such as 7α-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one, which are often very high in untreated CTX. MDPI+2Mayo Clinic Laboratories+2

11. CYP27A1 genetic testing – Sequencing the CYP27A1 gene looks for disease-causing variants; finding two harmful mutations (one in each copy) confirms the diagnosis and allows family carrier testing. Mayo Clinic Laboratories+2Wiley Online Library+2

12. Liver function tests – Blood tests such as bilirubin, ALT, AST, and alkaline phosphatase help check for liver damage or cholestasis, especially in infants or adults with chronic bile acid problems. Abdominal Key+2Ethernet University+2

13. Standard lipid profile – Total cholesterol may be normal or mildly changed, but other sterols and HDL can be abnormal; this profile helps rule out more common cholesterol disorders and supports the rare CTX picture. IJDVL+2Bangladesh Journals Online+2

14. Bone and vitamin D–related blood tests – Tests for vitamin D, calcium, phosphate, and bone turnover markers help assess bone health, since osteoporosis and fractures are frequent in CTX. Wikipedia+2SciSpace+2

Electrodiagnostic tests

15. Nerve conduction studies (NCS) – Electrodes stimulate nerves and measure how fast and strong signals travel; slowed conduction or reduced responses support the presence of peripheral neuropathy from sterol accumulation. Bangladesh Journals Online+1

16. Electromyography (EMG) – A small needle in muscles records electrical activity and can show chronic nerve damage or myopathy, helping to explain weakness and cramps in CTX patients. Radboud Repository+1

17. Electroencephalogram (EEG) – EEG records brain waves and is useful when seizures, unusual spells, or changes in awareness occur; abnormal patterns match the clinical history of epilepsy in some CTX cases. Springer Link+2Wikipedia+2

Imaging tests

18. Brain MRI – MRI often shows changes in the cerebellar dentate nuclei and other white-matter areas, sometimes with brain atrophy; these patterns are very helpful clues when doctors suspect CTX. PMC+2PMC+2

19. Tendon imaging (ultrasound or MRI of Achilles and other tendons) – Imaging of tendons can show thickening and fatty xanthomas made of cholestanol and cholesterol, even before they are very obvious on physical exam. ScienceDirect+2Nanbyo Lipid+2

20. Bone density scan (DEXA) and skeletal imaging – DEXA scanning measures bone mineral density and often shows osteoporosis; X-rays or other imaging may reveal fractures or deformities related to weak bones in long-standing disease. Wikipedia+2SciSpace+2

Non-pharmacological treatments

1. Early diagnosis and genetic counseling
   Once one person in a family is diagnosed, other relatives can be tested with blood tests and genetic testing. Early diagnosis allows treatment before serious brain damage happens. Genetic counseling helps the family understand inheritance, risks for future children, and options such as prenatal or pre-implantation testing.NCBI+1

2. Regular neurologic follow-up
   People with this disease need regular visits with a neurologist to check walking, balance, memory, mood, and seizures. The doctor adjusts medicines and therapies based on these findings. Close monitoring helps detect new problems early so that treatment can be changed quickly.PMC+1

3. Physiotherapy (physical therapy)
   Physiotherapy uses stretching, strengthening, balance, and gait exercises to keep muscles strong and joints flexible. It can reduce stiffness, improve walking, and lower fall risk. The therapist teaches home exercises that are safe and adapted to the person’s abilities.PMC+1

4. Occupational therapy
   Occupational therapists help the person manage daily activities such as dressing, bathing, writing, and using a computer. They suggest special tools (adaptive devices) and home changes, such as grab bars or raised toilet seats, to keep independence and safety.PMC+1

5. Speech and swallowing therapy
   If speech becomes slurred or swallowing is difficult, a speech-language therapist can teach exercises to strengthen mouth and throat muscles. They may suggest changing food texture or swallowing techniques to reduce choking and prevent lung infections.NCBI+1

6. Vision care and low-vision rehabilitation
   Early cataracts are common. Regular eye exams help decide the best time for cataract surgery. For any remaining vision problems, low-vision services provide magnifiers, contrast tools, and training to make reading and daily tasks easier.NCBI+1

7. Psychological support and counseling
   Living with a rare chronic disease can cause anxiety, sadness, or behavior changes. Counseling or psychotherapy supports both the patient and family, helps them cope with stress, and can improve treatment adherence and quality of life.PMC+1

8. Special education and cognitive rehabilitation
   Some people have learning problems or memory and attention difficulties. Special education, tutoring, and cognitive training (memory strategies, attention exercises) can support school performance and daily functioning. Starting these supports early gives the best long-term benefit.NCBI+1

9. Fall-prevention and home safety
   Because balance and coordination can be affected, the home should be checked for tripping hazards (loose rugs, wires, poor lighting). Simple changes and using mobility aids like canes or walkers can prevent fractures and head injuries.PMC+1

10. Regular monitoring of blood and imaging tests
    Blood tests (cholestanol, bile alcohols, liver enzymes, lipids) and sometimes MRI scans of the brain help doctors track how well treatment is working. Repeat testing guides dose adjustments of bile acids and other medicines.Frontiers+2NHS England+2

11. Healthy sleep hygiene
    Good sleep habits—regular sleep schedule, quiet dark bedroom, avoiding caffeine late in the day—can improve fatigue, mood, and cognitive function, which are often affected in this disease. Sleep problems should be discussed with the treating team.PMC+1

12. Avoiding smoking and limiting alcohol
    Smoking and heavy alcohol use can worsen liver damage, nerve injury, and heart risk. Avoiding these substances is especially important in a disease that already stresses the liver and nervous system.lipidjournal.com+1

13. Vaccination and infection prevention
    Infections can temporarily worsen neurologic symptoms and strain the liver. Staying up-to-date on routine vaccines (such as flu and pneumonia, according to local guidelines) and treating infections promptly helps protect overall health.NCBI+1

14. Balanced, low-cholesterol diet
    Diet cannot cure the enzyme defect, but reducing excess dietary cholesterol and saturated fat may help support lower lipid levels, together with bile-acid therapy and, when used, statins. A dietitian can design an individual meal plan.PMC+1

15. Weight management and regular gentle exercise
    Maintaining a healthy weight and doing light to moderate exercise (walking, swimming, cycling) can improve stamina, mood, and cardiovascular health, and can support mobility and balance. Exercise should be guided by the medical team.PMC+1

16. Support groups and rare-disease networks
    Connecting with other families through patient organizations or online communities for CTX or bile-acid disorders can reduce isolation, share practical tips, and help access expert centers and clinical trials.ScienceDirect+1

17. Family screening and cascade testing
    Since this is an autosomal recessive disease, brothers, sisters, and sometimes parents or cousins may be affected or carriers. Testing relatives allows early treatment before major problems appear.NCBI+1

18. Pregnancy and family-planning counseling
    Adults with CTX who want children should talk with a genetic counselor and high-risk obstetrician. They can discuss medication safety in pregnancy, partner carrier testing, and options like IVF with pre-implantation genetic testing.NCBI

19. Workplace or school accommodations
    Extra time for tasks, flexibility for medical appointments, and ergonomic modifications can help people maintain employment or education. Written plans with teachers or employers make expectations clear.PMC+1

20. Palliative and supportive care in advanced disease
    If severe neurologic disability develops despite treatment, palliative care teams can help manage pain, spasticity, feeding problems, and emotional stress, always focusing on comfort and dignity.PMC+1

Drug treatments

Safety note: Doses and schedules below are not personal medical advice. In practice, specialists adjust dose by age, weight, liver function, and lab results, following detailed product information and clinical guidelines.

1. Chenodeoxycholic acid (CDCA)
   CDCA is the gold-standard disease-specific treatment. It replaces the missing primary bile acid, lowers cholestanol and abnormal bile alcohols, and can stop or reverse symptoms, especially when started early in life. Dose is weight-based and adjusted with blood tests and liver monitoring. Common side effects include mild diarrhea or liver enzyme changes.NHS England+2Gimopen+2

2. Cholic acid (CHOLBAM®)
   Cholic acid is an FDA-approved bile acid for bile-acid synthesis disorders due to single-enzyme defects, which include sterol 27-hydroxylase deficiency. It supplies a primary bile acid, improves fat absorption, and can protect the liver. The FDA label recommends a weight-based daily dose, split once or twice daily, with regular liver tests. Possible side effects are diarrhea, liver enzyme elevation, or gallstones.FDA Access Data+2FDA Access Data+2

3. Chenodiol (CTEXLI™)
   Chenodiol is a bile acid recently approved by the FDA specifically for treatment of cerebrotendinous xanthomatosis in adults. It works similarly to CDCA by restoring bile-acid feedback and reducing cholestanol production. The label recommends starting at a low dose and adjusting slowly under liver-test monitoring, because high doses may injure the liver. Common side effects include diarrhea, abdominal discomfort, and reversible liver enzyme increases.FDA Access Data+1

4. Statins (for example, simvastatin)
   Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis. In CTX, they are sometimes added to bile-acid therapy to further lower cholesterol and cholestanol and shrink tendon xanthomas. They are taken once daily, usually in the evening. Side effects may include muscle pain, rare muscle breakdown, and mild liver-enzyme rises, so labs must be checked.ScienceDirect+1

5. Other statins (atorvastatin, rosuvastatin)
   If simvastatin is not tolerated or strong lipid lowering is needed, other statins may be chosen. The dose is titrated based on cholesterol and liver tests. Effects and side effects are similar across the class: muscle symptoms, rare liver injury, and interaction with some other drugs. The goal is to support long-term prevention of vascular disease and xanthomas.ScienceDirect+1

6. Antiepileptic drugs (for example, levetiracetam)
   Some people with CTX develop seizures. Levetiracetam is a commonly used antiepileptic with relatively few interactions. It reduces abnormal electrical activity in the brain. Dose is slowly increased until seizures are controlled and side effects such as irritability, sleepiness, or mood change are acceptable. Seizure control is important for safety and quality of life.NCBI+1

7. Other antiepileptics (valproate, lamotrigine, etc.)
   If seizures do not respond to one drug, other agents may be chosen based on seizure type, age, liver function, and pregnancy plans. These medicines calm brain over-activity. Each has specific side effects (for example, weight gain or tremor for valproate, rash risk for lamotrigine), so close monitoring is needed.NCBI+1

8. Baclofen (oral or intrathecal)
   Baclofen relaxes muscles by acting on GABA-B receptors in the spinal cord. It may reduce spasticity and muscle cramps in CTX. Oral baclofen is started at a low dose and increased slowly to avoid drowsiness and weakness. In severe cases, a pump can deliver baclofen directly around the spinal cord.PMC+1

9. Clonazepam
   Clonazepam is a benzodiazepine used for myoclonus (sudden jerks), seizures, and sometimes anxiety. It enhances GABA signaling in the brain. Because it can cause sleepiness, dependence, and balance problems, doctors use the lowest effective dose and try to avoid long-term high doses.PMC+1

10. Selective serotonin reuptake inhibitors (SSRIs, e.g., sertraline)
    Depression and anxiety are common in chronic neurologic diseases. SSRIs increase serotonin levels in the brain and can improve mood and anxiety over several weeks. Side effects include nausea, sleep changes, and, rarely, bleeding or serotonin syndrome with other drugs. Benefits must be balanced with drug interactions.PMC+1

11. Atypical antipsychotics (e.g., risperidone)
    If there are severe behavioral problems, psychosis, or agitation, low-dose atypical antipsychotics may be used. They adjust dopamine and serotonin pathways to calm thoughts and behavior. Possible side effects include weight gain, metabolic changes, and movement disorders, so careful monitoring is essential.PMC+1

12. Antiplatelet agents (e.g., low-dose aspirin when indicated)
    Because abnormal lipids can increase cardiovascular risk, some adults may be prescribed low-dose aspirin to help prevent blood clots, according to general cardiovascular guidelines. It works by reducing platelet stickiness. Risks include stomach irritation and bleeding, so it is not routine for every patient and must be individually assessed.lipidjournal.com+1

13. Fat-soluble vitamin supplements (A, D, E, K as medicines)
    If bile-acid problems impair fat absorption, vitamins A, D, E, and K may be given as prescription-strength preparations. They support vision, bone health, nerve function, and blood clotting. Blood levels are checked regularly to avoid both deficiency and toxicity.FDA Access Data+2FDA Access Data+2

14. B-complex vitamins (e.g., thiamine, B6, B12)
    B-vitamins support nerve health and energy metabolism. In some patients, especially with neuropathy or anemia, high-dose B vitamins may be prescribed. They are generally well tolerated but very high doses can cause nerve problems (B6) or masking of B12 deficiency, so monitoring is still needed.NCBI+1

15. Antidiarrheal agents (when needed)
    In infants and young children, chronic diarrhea may improve with bile-acid replacement, but sometimes antidiarrheal medicines and oral rehydration are used. These reduce stool frequency and prevent dehydration. Choice and dose depend on age and local guidelines.NCBI+1

16. Antispastic botulinum toxin injections
    For very focal spasticity (for example, in one limb), botulinum toxin can be injected into over-active muscles to relax them for several months. This can make stretching, bracing, and walking easier. Treatment must be repeated periodically.PMC+1

17. Pain medicines for orthopedic and tendon pain
    Non-opioid pain relievers (such as acetaminophen, and, when appropriate, NSAIDs) may be used to treat pain from xanthomas, joint strain, or after surgery. Doses follow general age- and weight-based guidance and must be used carefully in people with liver disease.PMC+1

18. Drugs for bladder or bowel control
    If neurologic damage affects bladder or bowel control, specific medicines (for example, anticholinergic drugs for bladder over-activity) may be used. They help improve continence and reduce infections, but can cause dry mouth, constipation, or confusion, especially in older adults.PMC+1

19. Anti-osteoporosis medicines (e.g., bisphosphonates when indicated)
    Long-term mobility problems and vitamin D problems may weaken bones. In adults with proven osteoporosis, medicines that slow bone breakdown may be considered along with vitamin D and calcium. These reduce fracture risk but require dental and kidney monitoring.FDA Access Data+1

20. Medicines in clinical trials
    Some centers study new ways to give bile acids, improve brain delivery, or combine treatments. Experimental drugs are only used in approved clinical trials with strict safety rules. Families interested in research should talk with specialized centers.Frontiers+1

Dietary molecular supplement

Supplements do not replace bile-acid therapy, but may support general health. Always discuss supplements with the medical team.

1. Omega-3 fatty acids (fish oil or algae oil) – support heart and brain health and may slightly improve blood lipids.lipidjournal.com+1

2. Vitamin D – supports bone strength and immune function, especially if sun exposure or absorption is low.FDA Access Data+1

3. Vitamin E – an antioxidant vitamin that protects cell membranes, particularly important when bile-acid problems cause fat-soluble vitamin loss.FDA Access Data+1

4. Vitamin A – supports vision and immune function but must be monitored to avoid toxicity.FDA Access Data+1

5. Vitamin K – helps normal blood clotting when fat absorption is reduced.FDA Access Data+1

6. B-complex (B1, B6, B12, folate) – supports nerve function, red-blood-cell production, and energy.NCBI+1

7. Coenzyme Q10 – a mitochondrial cofactor sometimes used off-label in neurologic disorders; evidence is limited but it may support energy metabolism.PMC+1

8. L-carnitine – helps transport fatty acids into mitochondria; sometimes used in metabolic and neuromuscular disorders to support energy, with limited evidence in CTX.PMC+1

9. Calcium supplements – support bones when vitamin D or mobility is low.FDA Access Data+1

10. Multivitamin tailored to liver/metabolic patients – provides a balanced mix of micronutrients; choice depends on local protocols and lab results.FDA Access Data+1

Regenerative / immunity-related and stem-cell-type approaches

There are no FDA-approved stem cell drugs or gene-therapy products specifically for sterol 27-hydroxylase deficiency today. The ideas below describe research directions and general immune support.

1. Hematopoietic stem cell transplantation (HSCT) – In theory, replacing bone-marrow cells that make the defective enzyme could help, but there is very little data in CTX, and HSCT has serious risks. It is not standard of care and would only be considered in research settings.PMC+1

2. Future gene-therapy approaches – Early research in similar metabolic diseases is exploring viral vectors to deliver a working gene to the liver. For CTX, this would aim to restore CYP27A1 activity. At present, this is theoretical and not available outside trials.Frontiers+1

3. Neuroprotective strategies – Trials in other neurologic diseases test drugs that protect nerves (for example, certain growth factors or anti-oxidants). For CTX, the best proven “neuroprotection” remains early and continuous bile-acid replacement to prevent further damage.NHS England+1

4. Immunizations as immune support – Keeping up-to-date with vaccines, including liver-related vaccines according to local guidelines, helps protect a person whose organs are already stressed by a chronic metabolic disease.NCBI+1

5. Good nutrition, sleep, and exercise as natural “immune boosters” – A balanced diet, enough sleep, and regular physical activity help the immune system work well and support recovery from infections and surgery.MD Searchlight+1

6. Participation in clinical trials – Some centers may test new regenerative or disease-modifying strategies in controlled trials. Joining such studies, when available, allows careful monitoring and contributes to future knowledge.Frontiers+1

Surgeries

1. Cataract surgery
   Many people with sterol 27-hydroxylase deficiency develop early cataracts. Removing the cloudy lens and placing an artificial lens can greatly improve vision and quality of life. Surgery is usually safe and is timed when cataracts begin to seriously affect daily activities.NCBI+1

2. Excision of tendon xanthomas
   Large fatty lumps on the Achilles or other tendons can be painful, limit movement, or cause cosmetic concerns. Surgical removal can reduce pain and improve walking or shoe fitting. However, xanthomas may recur if the underlying disease is not well controlled with bile-acid therapy.ScienceDirect+1

3. Orthopedic surgery for deformities
   If joint contractures, foot deformities, or scoliosis become severe, orthopedic surgery may help straighten bones, release tight tendons, or stabilize the spine. The purpose is to improve function, comfort, and ease of care.PMC+1

4. Feeding-tube placement
   In advanced disease with severe swallowing problems and weight loss, a gastrostomy tube may be placed into the stomach to allow safe feeding and medication delivery. This aims to prevent aspiration and malnutrition.PMC+1

5. Liver transplantation (rare)
   If there is severe, irreversible liver failure despite optimal bile-acid therapy, liver transplantation may be considered. A new liver should produce the missing enzyme, but transplantation carries major risks and is not routine for CTX; each case is individually reviewed.NCBI+1

Prevention of complications

Because the genetic defect cannot be prevented, the goal is to prevent complications and progression:

1. Newborn or early-life screening in at-risk families so treatment can start before symptoms.PMC+1

2. Lifelong, uninterrupted bile-acid therapy (CDCA, cholic acid, or chenodiol as prescribed) to keep cholestanol low.NHS England+1

3. Regular blood tests and MRI when advised to detect silent progression.Frontiers+1

4. Prompt treatment of cataracts and xanthomas to avoid long-term disability.NCBI+1

5. Control of cardiovascular risk factors (lipids, blood pressure, diabetes, smoking).lipidjournal.com+1

6. Vaccinations and rapid treatment of infections to avoid decompensation.NCBI+1

7. Physical activity and physiotherapy to maintain strength and balance.PMC+1

8. Psychological and social support to reduce depression, isolation, and non-adherence.PMC+1

9. Family genetic counseling to prevent unrecognized cases in relatives.NCBI+1

10. Care in specialized centers familiar with CTX and bile-acid disorders whenever possible.PMC+1

When to see doctors

You should see a doctor urgently (or go to emergency care) if there is sudden loss of vision, new or worsening seizures, severe confusion, sudden weakness, chest pain, or trouble breathing. These could be medical emergencies and not just part of the chronic disease.NCBI+1

Regular follow-up with the specialist team is also important if there is gradual change in walking, balance, memory, mood, or continence, or if new tendon lumps or jaundice appear. Any plan to become pregnant, major surgery, or change in medicines should also be discussed early with the team.PMC+1

Diet: what to eat and what to avoid

1. Focus on whole foods – plenty of vegetables, fruits, whole grains, beans, and lean protein to support heart and liver health.lipidjournal.com+1

2. Prefer healthy fats – use olive or other plant oils and eat nuts and seeds in moderation rather than large amounts of butter or lard.lipidjournal.com

3. Limit very high-cholesterol foods – such as organ meats and frequent large egg yolk portions; this supports lipid control along with medicines.lipidjournal.com+1

4. Choose lean meats and fish – fish rich in omega-3 may help heart health; choose grilled or baked, not deep-fried.lipidjournal.com

5. Avoid trans fats and heavily fried fast foods – they worsen cholesterol patterns and heart risk.lipidjournal.com+1

6. Ensure enough calcium and vitamin D – through dairy or fortified alternatives, plus vitamin D supplements if advised, to protect bones.FDA Access Data+1

7. Avoid excess sugar and soft drinks – to reduce fatty liver, obesity, and diabetes risk.lipidjournal.com+1

8. Limit or avoid alcohol – alcohol adds extra stress to the liver and nervous system.lipidjournal.com+1

9. Stay well hydrated – enough water supports circulation and kidney function, unless fluid is restricted for another reason.National Organization for Rare Disorders

10. Work with a dietitian – an experienced dietitian can personalize all these rules to age, weight, and lab results, especially when fat-soluble vitamin levels are abnormal.FDA Access Data+1

Frequently asked questions

1. Is sterol 27-hydroxylase deficiency curable?
   The underlying gene change cannot currently be cured, but disease-specific treatment with bile acids can greatly reduce symptoms and prevent progression in many patients, especially if started early and continued for life.NHS England+1

2. Why is early treatment so important?
   Early life is when most long-term brain and nerve damage can be prevented. Starting bile-acid therapy in infancy or childhood can stop toxic cholestanol from building up and can protect vision, movement, and thinking abilities.Frontiers+1

3. Can adults still benefit from treatment?
   Yes. Studies show that chenodeoxycholic acid and other bile-acid therapies can still lower cholestanol and improve or stabilize symptoms in adults, although damage that is already severe may not fully reverse.PubMed+1

4. How is the diagnosis confirmed?
   Doctors usually measure cholestanol and bile alcohols in blood and urine, and confirm the diagnosis by finding disease-causing variants in the CYP27A1 gene. Imaging such as brain MRI and tendon ultrasound can show typical changes.NCBI+1

5. Is this disease common?
   No. Sterol 27-hydroxylase deficiency is a rare autosomal recessive disorder. Many cases are missed or diagnosed late because symptoms are varied and resemble more common diseases.NCBI+1

6. Will all patients develop the same symptoms?
   No. Even within one family, some people may mainly have diarrhea and cataracts, while others develop tendon xanthomas or major neurologic problems. The severity is highly variable.NCBI+1

7. Do patients always need both bile-acid therapy and statins?
   Bile-acid replacement is the core disease-specific treatment. Statins are added only when lipid levels, xanthomas, or cardiovascular risk suggest a benefit. The decision is individualized by the specialist.ScienceDirect+2lipidjournal.com+2

8. How often are check-ups needed?
   In the first years after diagnosis or after changing therapy, visits may be every few months. Once stable, visits may be less frequent, but lifelong follow-up with labs and, sometimes, imaging is necessary.Frontiers+1

9. Can people with this condition have children?
   Many adults with CTX can have children, but they should receive genetic counseling and high-risk pregnancy care. Bile-acid and other medicines may need adjustment before and during pregnancy.NCBI

10. What is the life expectancy with treatment?
    With early diagnosis and good control, many people can live long lives, although exact numbers are not well known because the disease is rare. Late diagnosis with severe neurologic damage is linked to worse outcomes.PMC+1

11. Does diet alone ever replace medicine?
    No. Diet can support health and lipid control but cannot replace the missing enzyme or fully prevent toxic cholestanol buildup. Bile-acid therapy remains essential.NHS England+1

12. Are there special concerns for surgery or anesthesia?
    Yes. The anesthesiologist and surgeon should know about the disease, current medicines, and any neurologic or liver problems. They can adjust anesthesia drugs and monitor more closely during and after surgery.PMC+1

13. Can this disease affect the heart and blood vessels?
    Abnormal lipids and xanthomas can increase cardiovascular risk over time. Bile-acid therapy and statins, along with diet and lifestyle measures, are used to protect the heart and vessels.lipidjournal.com+1

14. Is there newborn screening for this disease?
    A few research programs and pilot studies are exploring newborn screening using bile-acid markers, but most places do not yet have routine newborn screening for CTX. Family-based testing remains very important.PMC+1

15. Where can families find more information and support?
    Families can seek specialized metabolic or genetic centers, rare-disease organizations, and dedicated CTX information sites run with medical oversight. These resources provide up-to-date treatment information, expert contacts, and community support.ScienceDirect+2National Organization for Rare Disorders+2

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December 21, 2025.

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