Homocystinuria caused by cystathionine beta-synthase deficiency is a rare genetic disease. In this condition, the body cannot use an amino acid called methionine in the normal way. Because of this, another substance called homocysteine builds up in the blood and tissues and becomes toxic for many organs. This problem mainly affects the eyes, bones, blood vessels, and brain.
The enzyme that does not work properly is called cystathionine beta-synthase (often shortened to CBS). This enzyme normally changes homocysteine into another substance called cystathionine, which then goes on to make cysteine. When CBS does not work, homocysteine and methionine go up, and cysteine goes down. This abnormal balance leads to damage to the lining of blood vessels, weak connective tissue, and problems in the nervous system.
Homocystinuria due to CBS deficiency is a rare inherited disorder where the body cannot properly break down the amino acid methionine, so homocysteine builds up in blood and urine. High homocysteine damages blood vessels, eyes, bones, and brain over time. Children may look tall and thin with long fingers, develop eye lens dislocation, learning problems, and dangerous blood clots. The condition is autosomal recessive, meaning both parents carry a faulty CBS gene. Treatment focuses on lowering homocysteine and keeping nutrition normal to prevent complications for life. [1][2][4]
This disease is inherited in an autosomal recessive way. That means a child gets one faulty copy of the CBS gene from each parent. Parents usually do not have symptoms; they are “carriers.” The disease can appear in childhood or later in life, and the severity can be very different from one person to another.
Other names
Homocystinuria caused by cystathionine beta-synthase deficiency is also known by several other names. These names describe the same basic condition:
Classical homocystinuria
CBS deficiency
Homocystinuria due to cystathionine beta-synthase deficiency
Homocystinuria, type I (CBS-related type)
All of these terms point to the same genetic enzyme problem in the CBS gene that leads to high homocysteine levels.
Types
There are a few useful ways to think about “types” of this disease. Doctors often group patients based on how they respond to vitamin B6 (pyridoxine), which is a helper vitamin for the CBS enzyme.
Vitamin B6–responsive type
In this type, the faulty enzyme still has some activity if it gets extra vitamin B6. When patients take high-dose vitamin B6, their homocysteine levels can drop a lot, and symptoms may improve or be prevented. This is usually a milder form and may be found later in life.Vitamin B6–partially responsive type
In this type, high-dose vitamin B6 helps a little but not enough on its own. Patients usually need both vitamin B6 and other treatments, such as a low-methionine diet and special medical foods, to keep homocysteine at a safer level.Vitamin B6–non-responsive type
Here, the enzyme does not respond to extra vitamin B6 at all. These patients usually have more severe disease, often starting in childhood, and they strongly need diet treatment, special formulas, and medicines such as betaine to help remove homocysteine.Early-onset (childhood) type
Signs such as poor growth, eye problems, or developmental delay may appear in infancy or early childhood. If not treated, the risk of blood clots and bone problems is high.Late-onset (adolescent or adult) type
Some people feel well as children and then first present as teens or adults, sometimes only with a blood clot, stroke, or lens dislocation. Because symptoms can be subtle, diagnosis is often delayed.
Causes
The main cause of this disease is a change (mutation) in the CBS gene. Below are 20 key causes and mechanisms that explain why the disease appears and why it damages the body.
CBS gene mutations
The primary cause is harmful variants in the CBS gene. These variants change the structure or function of the CBS enzyme so that it cannot process homocysteine properly.Autosomal recessive inheritance from carrier parents
A child must receive one faulty CBS gene from each parent to develop the disease. Parents are usually healthy carriers with one normal and one faulty copy. When both parents are carriers, each pregnancy has a one-in-four chance of producing an affected child.Reduced or absent CBS enzyme activity
Some mutations almost completely stop enzyme activity, while others reduce it. Lower activity means more homocysteine stays in the blood and tissues, which directly leads to toxicity.Accumulation of homocysteine in blood and tissues
Because homocysteine cannot be converted into cystathionine, it builds up. High homocysteine is directly harmful to blood vessels, nerves, and other tissues, and this is central to many symptoms.High methionine levels
The blocked pathway also causes methionine levels to rise, because methionine is upstream of homocysteine. High methionine further reflects the metabolic block and is used as a diagnostic clue in blood tests and newborn screening.Low cysteine levels
Because homocysteine cannot be converted onward, less cystathionine and cysteine are produced. Low cysteine may weaken protein and connective tissue, contributing to bone and eye problems.Endothelial (blood vessel lining) damage
Homocysteine directly injures the inner lining of arteries and veins. Damaged endothelium becomes “sticky,” promoting clot formation and narrowing of blood vessels.Increased tendency to form blood clots
High homocysteine makes blood more likely to clot by affecting clotting factors and platelets. This leads to deep vein thrombosis, pulmonary embolism, and stroke in untreated patients.Weak connective tissue and collagen cross-linking
Homocysteine interferes with cross-linking of collagen and other structural proteins. This weakens ligaments, bones, and the tissues that hold the eye lens in place, which explains the marfanoid features and lens dislocation.Lens zonule damage in the eye
The tiny fibers (zonules) that hold the lens are sensitive to abnormal connective tissue. Over time, they stretch or break, causing the lens to slip from its normal position (ectopia lentis) and leading to vision problems.Abnormal bone growth and osteoporosis
Disturbed collagen and bone matrix, together with nutrient imbalance, lead to long, thin bones, chest deformities, scoliosis, and loss of bone density with a higher fracture risk.Neurotoxicity to brain and nerves
High homocysteine and low cysteine can hurt brain cells and disturb neurotransmitters. This contributes to developmental delay, seizures, and behavior or psychiatric problems.Vitamin B6 (pyridoxine) deficiency or low intake
CBS is a vitamin B6–dependent enzyme. If a person with partial CBS activity also has low vitamin B6 intake, the enzyme works even less, so homocysteine rises further and symptoms may worsen.Low folate and vitamin B12 status
Folate and vitamin B12 are needed to remethylate homocysteine back to methionine in a different pathway. When these vitamins are low, the body has even less ability to handle homocysteine, so levels go higher.High methionine intake from diet
Eating a lot of methionine-rich foods (such as large amounts of meat, fish, or eggs) increases the load on the faulty pathway. In someone with CBS deficiency, this extra methionine is more likely to become excess homocysteine.Delay in diagnosis and treatment
When the condition is not found early, homocysteine stays high for many years. Long exposure increases the chance of serious complications like stroke, blindness, and severe bone disease.Poor adherence to low-methionine diet
For many patients, strict lifelong diet is needed. If the person often eats regular high-protein foods instead of their special diet, blood homocysteine rises and organ damage can progress.Inadequate use of betaine therapy when indicated
Betaine can help the body convert homocysteine back to methionine through an alternate pathway. If betaine is not used when needed, or doses are too low, homocysteine may remain dangerously high.Other genetic modifiers in homocysteine metabolism
Variants in other genes, such as those for the enzyme MTHFR, can further reduce the body’s ability to handle homocysteine. In a person with CBS deficiency, this can worsen the biochemical imbalance.Intercurrent illness or stress without treatment adjustment
Periods of illness, poor food intake, or metabolic stress can upset the balance of amino acids and vitamins. If diet and medicines are not adjusted, homocysteine may spike higher during these times.
Symptoms
Symptoms can be very different from person to person. Some people show many features; some show only a few. Below are 15 common symptoms and signs.
Severe short-sightedness (high myopia)
Many patients develop very strong short-sightedness, often in childhood. They may need thick glasses and have trouble seeing distant objects clearly. This is related to changes in the shape and structure of the eye.Lens dislocation (ectopia lentis)
The eye lens can slip from its normal central position because the supporting fibers are weak. This can cause blurred vision, double vision, glare, or even sudden vision loss if the lens moves a lot.Glaucoma or increased eye pressure
Changes in the eye, including lens movement, can disturb the flow of fluid inside the eye and raise pressure. Over time, this can damage the optic nerve and lead to loss of sight if not treated.Marfanoid body shape
Many patients look tall and thin, with long arms, long legs, long fingers, and a narrow chest. This “marfanoid” appearance happens because the connective tissues are weak and stretch more than normal.Chest and spine deformities
The breastbone can point outward (pectus carinatum) or inward (pectus excavatum), and the spine can curve sideways (scoliosis). These changes build up slowly over years as bones grow in an abnormal way.Osteoporosis and bone pain
Low bone density is common, even in young people with the disease. Bones become fragile and may break easily after minor falls. Some people develop chronic bone or back pain.Blood clots in veins (deep vein thrombosis)
Patients with untreated homocystinuria have a high risk of clots in the deep veins of the legs or other sites. Signs can include swelling, pain, and redness of a limb. These clots can travel to the lungs and be life-threatening.Stroke or other arterial clots
Clots can also form in arteries that supply the brain or other organs. This may cause stroke, sudden weakness, trouble speaking, or vision problems. In some adults, a stroke is the first sign that leads to diagnosis.Developmental delay and learning problems
If the disease is not treated early, children may sit, walk, or speak later than usual. Many have learning difficulties at school and may need extra educational support.Intellectual disability
Some untreated patients develop lasting problems with thinking, understanding, and daily living skills. Early treatment can reduce this risk, which is why newborn screening and early diagnosis are very important.Seizures (fits)
Abnormal electrical activity in the brain can cause seizures. These may look like staring spells, stiffening or jerking movements, or sudden loss of awareness. Seizures are more common in patients with high homocysteine for a long time.Behavior and psychiatric problems
Some people develop anxiety, depression, mood swings, or psychosis-like symptoms. These changes may be due to direct effects of high homocysteine on the brain and to the stress of living with a chronic disease.Fair hair and light skin (hypopigmentation)
Many patients have lighter hair and skin than other family members. This may be related to changes in amino acid and pigment pathways affected by the metabolic block.Flushed cheeks and skin changes
A reddish color of the cheeks (malar flush) and a net-like pattern on the skin (livedo reticularis) are reported in some patients. These signs reflect changes in small blood vessels and circulation.Pancreatitis and other organ problems
A few patients develop inflammation of the pancreas or other internal organs, possibly linked to small vessel damage and abnormal clotting. This can cause severe abdominal pain and requires urgent care.
Diagnostic tests
Doctors use a mix of clinical examination and special tests to diagnose homocystinuria caused by cystathionine beta-synthase deficiency. The main goal is to show high homocysteine, high methionine, low or abnormal CBS activity, and a disease-causing change in the CBS gene.
Physical exam tests
Full general physical examination
The doctor checks height, weight, body proportions, chest shape, spine, joints, and skin. They look for marfanoid build, chest deformities, scoliosis, light skin, and flushed cheeks. These clues, together with family history, can suggest classical homocystinuria.Eye and vision examination
A simple eye exam with a light and an eye chart can show poor vision and signs that the lens is out of place. The doctor may notice unusual reflections or an abnormal lens position when shining light in the eyes.Joint and skeletal examination
The doctor examines the joints for unusual flexibility or stiffness and inspects fingers, arms, legs, and chest. Long, thin fingers and abnormal chest or spine curves support the suspicion of a connective tissue problem like CBS deficiency.Neurological examination
The doctor tests muscle strength, reflexes, coordination, and balance. Any weakness, abnormal reflexes, or coordination problems may point to nervous system involvement from long-standing high homocysteine levels.
Manual (bedside) tests
Visual acuity testing (eye chart)
Reading letters or symbols at different distances helps measure how well a person sees. Very poor distance vision, especially in a young child, raises suspicion of high myopia or lens problems linked to homocystinuria.Joint flexibility (Beighton score or similar)
Simple maneuvers, such as bending the thumb to the forearm or hyper-extending the knees, help measure joint looseness. A high flexibility score may show that connective tissues are weak, as seen in this disease.Gait and balance tests
Tasks like walking in a straight line, standing on one foot, or heel-to-toe walking help assess balance and coordination. Abnormal results can reflect neurological or skeletal problems from long-standing disease.Developmental and cognitive screening
Simple age-appropriate questions and tasks, or short screening tools, help check speech, understanding, memory, and learning abilities. Delays or difficulties suggest possible brain effects of high homocysteine.
Laboratory and pathological tests
Plasma total homocysteine level
This is the key laboratory test. A blood sample is taken and total homocysteine is measured. In untreated CBS deficiency, levels are usually very high, often many times above the normal range, making this a frontline diagnostic tool.Plasma methionine concentration
Blood methionine is often elevated in classical homocystinuria. Measuring methionine together with homocysteine helps distinguish CBS deficiency from other causes of high homocysteine.Urine homocystine measurement
Homocystine (the oxidized form of homocysteine) can appear in the urine. Older screening methods used a cyanide–nitroprusside test to detect it. Modern labs may use more specific methods, but finding homocystine in urine strongly supports the diagnosis.Plasma amino acid profile by tandem mass spectrometry
This test looks at many amino acids at once using a single blood sample. Newborn screening programs often use this method. A pattern of high methionine with suggestive findings may trigger further testing for CBS deficiency.Vitamin B6, B12, and folate levels
Measuring these vitamins helps rule out other causes of high homocysteine and shows if vitamin levels are low. It also guides therapy, since extra vitamin B6, B12, and folate are part of standard treatment in many patients.CBS enzyme activity assay
In some centers, enzyme activity can be measured in cultured skin cells (fibroblasts) or blood cells. Very low or absent CBS activity supports the diagnosis and can help study how severe the enzyme defect is.Molecular genetic testing of the CBS gene
DNA testing looks for disease-causing variants in the CBS gene. Finding two harmful variants (one from each parent) confirms the genetic diagnosis, helps with family planning, and allows carrier testing of relatives.
Electrodiagnostic tests
Electroencephalogram (EEG)
If a person has seizures or suspected seizure activity, an EEG can record the brain’s electrical patterns. Abnormal spikes or waves support a diagnosis of epilepsy related to the underlying metabolic disease.Nerve conduction studies and electromyography (EMG)
When there are signs of nerve or muscle involvement, these tests measure how fast nerves carry signals and how muscles respond. Abnormal results may show that long-standing high homocysteine has affected peripheral nerves.
Imaging tests
Slit-lamp biomicroscopy of the eye
An eye specialist uses a slit-lamp microscope to look closely at the front of the eye. This exam shows whether the lens is out of place, its direction of movement, and any other eye changes caused by homocystinuria.Brain MRI (magnetic resonance imaging)
MRI gives detailed pictures of the brain. It can show old strokes, white matter changes, or other structural problems caused by clots or long-term metabolic injury. This helps explain neurological symptoms.Skeletal X-rays and bone density scan (DXA)
X-rays of the spine, chest, and long bones reveal scoliosis, chest deformities, and thinning of bones. A bone density scan (DXA) measures how strong the bones are and can detect osteoporosis early in patients with CBS deficiency.
Non-pharmacological treatments (therapies and others)
Low-methionine, protein-restricted diet
A special diet limits natural protein (meat, fish, eggs, dairy) because these foods contain methionine, which turns into homocysteine. Dietitians design a safe daily protein target for age, weight and growth. This diet is life-long and must be very exact. It is the main non-drug treatment for people who are not fully responsive to vitamin B6. [1][2][5]Special medical formula (methionine-free amino acid mixture)
Many patients drink a medical formula that contains all essential amino acids except methionine. This allows normal growth while keeping methionine and homocysteine low. The formula also contains vitamins and minerals to prevent nutritional gaps from protein restriction. It is usually taken several times a day with meals. [2][5][4]Cysteine enrichment in the diet
Because the blocked pathway normally makes cysteine from methionine, cysteine can become “conditionally essential”. Extra cysteine from formula or food helps protein building and antioxidant defenses without raising homocysteine, and is part of many dietary protocols. [2][5][1]Regular metabolic monitoring and clinic visits
Patients need frequent blood tests to measure total homocysteine, methionine, vitamin levels and growth. Clinicians adjust diet, betaine and vitamins based on these results. Close, long-term follow-up in a metabolic center is critical to prevent eye, bone and clotting problems. [1][2]Genetic counseling for families
Genetic counselors explain inheritance, carrier testing and recurrence risk for future pregnancies. They help parents understand options such as prenatal diagnosis or preimplantation genetic testing, and support extended family screening when appropriate. [1][4]Newborn screening and early treatment
In regions where newborn screening includes homocystinuria, babies can be diagnosed before symptoms. Early diet and vitamin treatment greatly lowers risk of eye dislocation, thrombosis and learning problems, and improves long-term outcomes. [2][4]Ophthalmology follow-up and visual rehabilitation
Regular eye exams detect lens dislocation, short-sightedness and glaucoma early. Glasses, contact lenses, low-vision aids and timely surgery protect vision and quality of life. Ophthalmologists are core members of the care team. [1][2]Physical therapy and orthopedic follow-up
Tall, thin body habitus, scoliosis and chest deformities are common. Physiotherapy improves posture, muscle strength and joint stability. Orthopedic specialists monitor spine, chest and bone density, and decide when braces or surgery are needed. [1][2]Lifestyle measures to lower blood-clot risk
People are advised to avoid prolonged immobility, maintain healthy weight, stop smoking and stay well hydrated, especially during travel or illness. These simple habits support the main medical treatments in lowering thromboembolism risk. [2][4]Compression stockings and movement during long travel
On long flights or car trips, using compression stockings, walking regularly and doing calf exercises help keep blood flowing and reduce deep vein thrombosis risk in susceptible patients. [2][4]Pregnancy planning with high-risk obstetric care
Women with CBS deficiency need careful planning before pregnancy with diet, vitamins and betaine optimized. During pregnancy they need close monitoring and sometimes preventive blood thinners to reduce clot risk, guided by specialists. [1][2][21]Education about warning signs of thrombosis and stroke
Families learn to recognize sudden leg pain and swelling, chest pain, shortness of breath, or sudden weakness and speech problems, so they can seek emergency care quickly. Early action saves lives. [1][2][4]Neuropsychological assessment and learning support
Some patients may have developmental delay or learning difficulties. Early cognitive testing, special education support and speech therapy help children reach their full potential at school. [1][4]Psychological counseling and support groups
Living with a rare lifelong condition can be stressful. Counseling and patient organizations provide emotional support, help families cope with diet and treatments, and connect them with others facing the same disease. [4][27]Standard vaccination and infection prevention
Routine childhood and adult vaccines are important, as serious infections can trigger dehydration, reduced mobility and higher clot risk. Good hygiene and early treatment of illness also help. [1][4]Careful peri-operative planning
If surgery is needed for any reason, the anesthetic team must know about homocystinuria. They plan good hydration, early mobilization and sometimes preventive anticoagulation to reduce clot risk around the operation. [2][19]Avoidance of certain risk-increasing medicines
Some estrogen-containing contraceptives and other drugs may increase blood-clot risk. Specialists help choose safer contraception and review medicines regularly, especially in adolescence and adulthood. [2][4]Bone health measures
Adequate calcium, vitamin D, weight-bearing exercise and sometimes bone-density monitoring help counteract osteoporosis and fracture risk seen in some patients with CBS deficiency. [1][2]Multidisciplinary care coordination
A metabolic pediatrician or adult metabolic physician coordinates dietitian, ophthalmologist, hematologist, orthopedist and psychologist inputs. This team approach reduces complications and improves quality of life. [1][2][19]Patient-held emergency and information plans
Written emergency cards and care plans explain the diagnosis, usual treatments and emergency advice. They guide health professionals who are unfamiliar with homocystinuria, especially in emergencies or new hospitals. [1][4]
Drug treatments (based on FDA / guideline evidence)
(Doses are individualized; always follow specialist and official prescribing information, such as FDA labels.)
Pyridoxine (vitamin B6)
High-dose pyridoxine is first-line in B6-responsive CBS deficiency. It acts as a cofactor to boost remaining enzyme activity and can dramatically lower homocysteine. About half of patients show some response. Dose and monitoring are specialist decisions to avoid nerve toxicity. [1][2][23]Pyridoxal-5-phosphate (active vitamin B6)
In some patients who do not tolerate or respond well to regular pyridoxine, the active form pyridoxal-5-phosphate may be tried. It supports enzyme function in a similar way but is used under close expert guidance. [2][23]Betaine anhydrous (Cystadane and generics)
Betaine is an FDA-approved drug for homocystinuria. It donates a methyl group to remethylate homocysteine back to methionine, significantly lowering plasma homocysteine, especially in B6-non-responsive patients. It is taken orally as a powder mixed with liquid or food, usually twice daily. Side effects can include gastrointestinal discomfort and high methionine, so levels must be monitored. [2][3][5][22]Folic acid (folate)
Folate is needed for one-carbon metabolism and helps remethylate homocysteine to methionine via the folate-dependent pathway. Low folate can worsen homocysteine. Many treatment plans include daily folic acid to optimize this pathway, with doses chosen to avoid masking B12 deficiency. [1][2]Folinic acid (leucovorin)
Folinic acid is an active folate form sometimes used when absorption or metabolism of folic acid is a concern. It supports remethylation pathways and may be used alongside other treatments to keep homocysteine lower. [1][2]Vitamin B12 (hydroxocobalamin or cyanocobalamin)
Vitamin B12 is another cofactor in homocysteine remethylation. Deficiency raises homocysteine even more. In CBS deficiency, injections or high-dose oral B12 are often used to ensure this pathway works as well as possible, especially if lab tests show low or borderline levels. [1][2]Cysteine or N-acetylcysteine (as a medicinal product)
Cysteine may be provided medicinally (or via formula) to replace what the blocked pathway would normally produce, supporting protein synthesis and antioxidant defenses. N-acetylcysteine is an acetylated form with antioxidant effects, used cautiously and under specialist guidance. [2][5]Low-dose aspirin (antiplatelet therapy)
In older children and adults at high risk of thrombosis, low-dose aspirin may be prescribed to reduce platelet activation and clot formation. Its use is carefully weighed against bleeding risk and other clot-prevention measures. [2][19]Low-molecular-weight heparin (LMWH)
During high-risk periods such as surgery, pregnancy or after previous clots, LMWH injections may be used temporarily to prevent new thrombosis. Dose depends on weight and kidney function, and is monitored by hematology or high-risk obstetric teams. [2][21]Vitamin K antagonists (e.g., warfarin) – selected cases
In some adults with a history of serious clots, long-term anticoagulation with warfarin may be considered. This requires regular blood tests (INR) and careful management of diet and interacting medicines, always under specialist supervision. [2][19]Direct oral anticoagulants (DOACs) – individualized, off-label in some settings
Some clinicians may consider DOACs such as rivaroxaban or apixaban for secondary prevention of venous thrombosis, based on overall risk–benefit. Evidence in rare inherited thrombophilias is limited, so decisions are highly individualized. [2][19]Antihypertensive drugs, if needed
If a patient develops high blood pressure, standard blood-pressure medicines (such as ACE inhibitors) may be used to reduce vascular strain and stroke risk. These treat associated risk factors rather than the enzyme defect itself. [4][19]Statins for abnormal lipids
If cholesterol and triglycerides are high, statins or other lipid-lowering drugs may be added to reduce cardiovascular risk. This is common adult preventive care but becomes more important when homocysteine is also high. [4][19]Antiepileptic medicines (e.g., levetiracetam) for seizures
If seizures occur because of prior strokes or brain involvement, modern anti-seizure medicines are used according to standard neurology guidelines. The choice minimizes interactions with anticoagulants and other long-term therapies. [1][4]Analgesics (e.g., paracetamol/acetaminophen) for pain
Simple pain relievers may be used after surgery, in bone or joint pain, or during headaches. Non-steroidal anti-inflammatory drugs are used carefully when clot risk and other medicines are considered. [4]Vitamin D and calcium medicinal supplements
If blood or bone tests show low vitamin D or poor bone health, vitamin D and calcium may be given medicinally to improve bone strength, along with diet and exercise. [1][2]Multivitamin preparations
Some patients receive tailored multivitamin preparations (without excess pyridoxine if testing is planned) to prevent deficiencies created by protein-restricted diets. Contents and doses are chosen by the metabolic team. [2][9]Investigational enzyme therapies (e.g., pegtibatinase – in trials)
New therapies attempt to replace or mimic CBS activity using modified enzymes. These are still in clinical trials and not yet standard care or widely approved. They are only used in research settings with strict monitoring. [23][15]Emerging gene-based therapies (research only)
Gene therapy aims to correct or replace the faulty CBS gene in liver cells, addressing the root cause. This remains experimental, but is a focus of future treatment research. [23][15]Supportive medicines around surgery or pregnancy
During surgery, pregnancy or serious illness, temporary medicines such as IV fluids, anticoagulants, oxygen and other supportive drugs are used to protect the patient while the underlying metabolic treatment continues. [2][21][19]
Dietary molecular supplements
(Many overlap with medicines; always discuss with a metabolic dietitian before use.)
Betaine (as a nutritional methyl donor)
When prescribed, betaine provides methyl groups to convert homocysteine back to methionine, lowering toxic homocysteine levels. It is both a drug and a functional nutrient, and must be carefully dosed and monitored to avoid very high methionine. [2][3][22]Folate (folic acid) supplement
Folate supports the folate-dependent remethylation pathway. Ensuring adequate folate intake through supplements and diet helps homocysteine metabolism work more efficiently, especially when combined with B12 and betaine treatments. [1][2]Vitamin B12 supplement
Even mild B12 deficiency can significantly raise homocysteine. Oral or injectable B12 ensures the methionine synthase pathway functions well, complementing other treatments and protecting nerves. [1][2]Vitamin B2 (riboflavin)
Riboflavin is involved in folate and homocysteine metabolism through its role in the MTHFR enzyme. Some protocols use riboflavin to optimize these pathways, although evidence is more indirect than for B6, folate and B12. [2][23]Vitamin B1 (thiamine) and B-complex
Balanced B-complex supplements support multiple enzymes in energy and amino acid metabolism. In strict diets, they help prevent general B-vitamin deficiency and support overall metabolic health. [1][4]Omega-3 fatty acids (fish oil)
Omega-3 fatty acids support heart and blood vessel health by improving lipid profiles and reducing inflammation. While they do not correct the enzyme defect, they may lower cardiovascular risk alongside homocysteine-lowering treatments. [4][19]Choline
Choline participates in methyl-group metabolism and phospholipid synthesis. Adequate choline intake through diet or supplements may support liver health and one-carbon metabolic pathways connected to homocysteine balance. [5][23]Vitamin D
Vitamin D supports bone mineralization and immune function. In CBS deficiency, low vitamin D plus low dietary protein can worsen osteoporosis. Supplementation helps maintain bone strength and general health. [1][2]Calcium
Calcium supplements may be used when dietary calcium is limited due to protein restriction or dairy avoidance, supporting bones and muscle function in growing children and adults. [1][2]Zinc and trace elements
Zinc and other trace minerals are important for enzyme activity, immune defense and wound healing. Special formulas usually include them, but additional supplements may be used if blood tests show low levels. [1][2]
Immunity-booster, regenerative and stem-cell-related approaches
General immune support rather than “strong boosters”
For CBS deficiency, there are no specific “immune-booster drugs” proven to improve homocysteine control. Doctors focus on good nutrition, vaccines, sleep, stress management and avoiding smoking to keep immunity healthy in a balanced way. [1][4]Multivitamin and micronutrient support
Adequate vitamins A, C, D, E, B-complex, zinc and selenium help the immune system work properly. In CBS patients on restrictive diets, clinicians may use tailored multivitamins to prevent deficiencies that could weaken immune responses. [1][2]Standard childhood and adult vaccination
Routine vaccines (for example, flu and pneumococcal vaccines in adults where recommended) reduce serious infections that might trigger dehydration, immobility and clot formation. This is a practical, evidence-based way to protect health. [1][4]No established stem cell drug therapy for CBS deficiency yet
There are currently no approved stem cell drugs specifically for homocystinuria due to CBS deficiency. Hematopoietic stem cell transplants used in some metabolic diseases are not standard for this condition. Any such approach remains experimental. [1][23]Liver-directed cell or gene therapies (research)
Because CBS enzyme is mainly in the liver, possible future treatments include hepatocyte transplantation or gene therapy to replace or repair liver cells. These approaches are still under investigation and not part of routine care. [15][23]Healthy lifestyle to support tissue repair and resilience
Regular exercise within safe limits, balanced energy intake, good sleep and stress reduction support natural tissue repair and general resilience, even though they cannot correct the enzyme defect itself. [4][19]
Surgeries and procedures
Lens extraction with intraocular lens implantation
Dislocation of the eye lens (ectopia lentis) is common. When vision is significantly impaired or there is risk of glaucoma, surgeons may remove the displaced lens and insert an artificial one to improve sight and prevent complications. [1][2]Glaucoma and retinal procedures
If high eye pressure or retinal complications develop, additional eye surgeries or laser procedures may be needed to protect remaining vision, tailored to each patient’s eye findings. [1][2]Orthopedic surgery for skeletal deformities
Severe scoliosis, chest wall deformities or disabling bone changes sometimes require surgery. Operations aim to improve posture, lung capacity, pain and function, especially when bracing and physiotherapy are not enough. [1][2]Vascular surgery or interventional radiology for thrombosis
In life-threatening blood clots (such as large deep vein thrombosis or pulmonary embolism), specialized procedures like thrombectomy or catheter-directed therapies may be needed alongside anticoagulant drugs. [2][19]Liver transplantation (very selected cases)
Liver transplantation can, in theory, provide new liver cells with a working CBS enzyme and has been reported rarely. Because of transplant risks and life-long immunosuppression, it is reserved for very special situations and is not routine treatment. [1][2]
Prevention strategies
Early newborn screening where available. [1][2]
Lifelong follow-up in a metabolic center. [1][2][19]
Strict adherence to low-methionine diet and medical formula. [2][5]
Regular use of prescribed pyridoxine, betaine and vitamins. [2][3][23]
Avoiding smoking and second-hand smoke exposure. [4][19]
Maintaining healthy weight, regular moderate exercise and good hydration. [4][19]
Careful planning for surgery, pregnancy and long travel with thrombosis prevention. [2][21]
Routine vaccinations and prompt treatment of infections. [1][4]
Regular eye, bone and cardiovascular check-ups to detect early changes. [1][2]
Family genetic counseling and carrier testing where appropriate. [1][4]
Each measure adds a layer of protection to limit long-term damage from high homocysteine.
When to see doctors
People with homocystinuria due to CBS deficiency should have regular scheduled visits with a metabolic specialist and dietitian, usually several times a year in childhood and at least yearly in stable adults. These visits check blood tests, growth, diet, eye health and clot risk, and allow early adjustment of treatment plans. [1][2]
Urgent medical review is needed if there are signs of blood clots, such as new leg swelling and pain, sudden chest pain, difficulty breathing, coughing blood, sudden severe headache, weakness, facial drooping or difficulty speaking. These can be stroke or pulmonary embolism symptoms and require emergency care. [1][2][4]
You should also contact the care team promptly if the person is vomiting, has severe diarrhea, cannot keep diet or medicines down, or is unusually sleepy or confused, because dehydration and illness can worsen metabolic control and clot risk. [1][2]
Women with this condition should see both their metabolic specialist and an experienced obstetrician before trying for pregnancy, as treatment and clot prevention may need to be adjusted before conception and throughout pregnancy. [1][2][21]
Diet: what to eat and what to avoid
Eat measured amounts of low-protein foods
Fruits, many vegetables and some grains in carefully weighed portions provide energy, vitamins and fiber while keeping methionine intake controlled. [2][27]Use prescribed low-protein specialty foods
Low-protein breads, pastas and baking mixes help provide variety and calories without excess methionine, and are often essential in daily menus. [2][27]Take medical formula exactly as prescribed
The methionine-free amino acid mixture (formula) is the main source of safe protein, vitamins and minerals. Skipping formula can cause poor growth and weakness. [1][2]Limit or avoid natural high-protein foods (unless told otherwise)
Meat, fish, eggs, cheese, regular milk, nuts and many legumes are high in methionine and usually restricted. Amounts allowed depend on individual tolerance and B6 responsiveness. [1][2]Choose healthy fats
Oils rich in unsaturated fats and omega-3 (like canola and some vegetable oils) are preferred over saturated fats to help protect heart and blood vessels. [4][19]Include adequate fruits and vegetables
A wide range of fruits and vegetables adds vitamins, minerals and antioxidants, supporting general health within the limits set by the dietitian. [2][27]Avoid crash diets and fasting
Extreme dieting, fasting or very low-calorie plans can trigger muscle breakdown and worsen homocysteine levels, so weight changes must be gradual and supervised. [2][4]Be careful with high-protein “health” products
Protein shakes, bars, bodybuilding supplements and some “energy” foods often contain large amounts of methionine and should be avoided unless specifically approved by the metabolic team. [2][4]Read labels for hidden protein and vitamins
Foods enriched with pyridoxine (B6) may need to be avoided shortly before certain tests, and protein sources may appear in unexpected products. Dietitians teach families how to read labels carefully. [2][9]Stay in close contact with the metabolic dietitian
Diet needs change with age, growth, pregnancy and illness. Regular review helps keep homocysteine low while maintaining good nutrition and quality of life. [1][2][27]
Frequently asked questions (FAQs)
Is homocystinuria due to CBS deficiency curable?
At present, it is not curable, but it is treatable. With early diagnosis, strict diet, vitamins and betaine, many people can live active lives and greatly reduce complications. [1][2]What is the main goal of treatment?
The main goal is to keep total homocysteine in blood as low as safely possible while maintaining normal growth and nutrition. This helps prevent eye problems, bone weakness, learning issues and blood clots. [1][2][5]What is the difference between B6-responsive and B6-non-responsive disease?
In B6-responsive patients, high-dose pyridoxine activates enough CBS enzyme to lower homocysteine significantly. B6-non-responsive patients need stricter diet and usually betaine because the enzyme does not respond well to B6. [1][2][23]Why is betaine so important in many patients?
Betaine provides an alternative pathway to remove homocysteine by remethylating it to methionine. Studies show it can significantly lower homocysteine in B6-non-responsive patients when combined with diet control. [2][3][5][22]Can a child with this condition live a normal life?
Many children diagnosed early through newborn screening and treated properly can attend regular school, play sports and live fairly typical lives, although they must follow their diet and medicines carefully. [1][2][27]What happens if treatment is poor or stopped?
Without good control, the risk of lens dislocation, osteoporosis, learning difficulties and dangerous blood clots (deep vein thrombosis, stroke, pulmonary embolism) increases, sometimes with life-threatening results. [1][2][18]Can adults be diagnosed for the first time?
Yes. Some mildly affected people are only diagnosed after a blood clot or eye problem in adulthood. Even then, treatment can reduce further risks, so testing is important when doctors suspect homocystinuria. [1][2][19]Is regular exercise safe?
Moderate, regular exercise is usually encouraged, as it supports heart, bone and mental health. However, extreme exertion, dehydration and immobility after exercise should be avoided, and plans should be discussed with the care team. [4][19]Why are eye checks needed if vision seems fine?
Lens dislocation and other eye issues may develop slowly and be missed until advanced. Regular eye exams allow early treatment to protect vision and prevent complications like glaucoma. [1][2]Do siblings need testing?
Because the condition is inherited, brothers and sisters of an affected child should be offered testing. Early diagnosis allows early treatment and better outcomes if they are also affected. [1][4]Can women with CBS deficiency have safe pregnancies?
Yes, many can with careful planning. Diet, vitamins, betaine and sometimes anticoagulation are adjusted by a metabolic specialist and high-risk obstetrician to protect both mother and baby. [1][2][21]Are there new treatments being researched?
Research is ongoing into improved enzyme therapies, gene-based treatments and better ways to individualize diet and medicines. These may further improve outcomes in the future but are not yet widely available. [15][23]Is mental health support important?
Yes. Life-long diet, frequent blood tests and fear of complications can be stressful. Counseling and peer support can improve coping, treatment adherence and overall quality of life. [4][27]Can people with this condition drink alcohol?
Small amounts of alcohol may be allowed for some adults, but excess alcohol can worsen nutrition, increase falls and affect liver function. Patients should always ask their specialist before drinking. [4][19]Where can families find reliable information and support?
Trusted sources include metabolic clinics, national rare-disease organizations, patient support groups and expert-written resources such as GeneReviews, international guidelines and reputable hospital websites. [1][2][4][26]
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: January 27, 2025.
