Homocystinuria
Cystathionine beta-synthase deficiency; CBS deficiency; HCYHomocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. Amino acids are the building blocks of all proteins in the body.
Metabolism
Metabolism refers to all the physical and chemical processes in the body that convert or use energy, such as:BreathingCirculating bloodControlling bo...
Read Article Now Book Mark ArticleAmino acid
Amino acids are molecules that combine to form proteins. Amino acids and proteins are the building blocks of life. When proteins are digested or bro...
Read Article Now Book Mark ArticleCauses
Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected.
Autosomal recessive
Autosomal recessive is one of several ways that a genetic trait, disorder, or disease can be passed down through families. An autosomal recessive dis...
Read Article Now Book Mark ArticlePeople with homocystinuria have several physical features in common with Marfan syndrome, including skeletal and eye changes.
Marfan syndrome
Marfan syndrome is a disorder of connective tissue. This is the tissue that strengthens the body's structures. Disorders of connective tissue affect...
Read Article Now Book Mark ArticleSymptoms
Newborn infants appear healthy. Early symptoms, if present, are not obvious.
Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition.
Failure to thrive
Failure to thrive refers to children whose current weight or rate of weight gain is much lower than that of other children of similar age and sex....
Read Article Now Book Mark ArticleVisual problems
There are many types of eye problems and vision disturbances, such as: Halos Blurred vision (the loss of sharpness of vision and the inability to see...
Read Article Now Book Mark ArticleOther symptoms include:
- Chest deformities (pectus carinatum, pectus excavatum)
Pectus carinatum
Pectus carinatum is present when the chest protrudes over the sternum. It is often described as giving the person a bird-like appearance.
Read Article Now Book Mark ArticlePectus excavatum
Pectus excavatum is a medical term that describes an abnormal formation of the rib cage that gives the chest a caved-in or sunken appearance....
Read Article Now Book Mark Article - Flush across the cheeks
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High arches of the feet
High arches of the feet
High arch is a foot arch that is raised more than normal. The arch runs from the toes to the heel on the bottom of the foot. It is also called pes ...
Read Article Now Book Mark Article - Intellectual disability
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Knock knees
Knock knees
Knock knees are condition in which the knees touch, but the ankles do not touch. The legs turn inward.
Read Article Now Book Mark Article - Long limbs
- Mental disorders
- Nearsightedness
- Spidery fingers (arachnodactyly)
Arachnodactyly
Arachnodactyly is a condition in which the fingers are long, slender, and curved. They look like the legs of a spider (arachnid).
Read Article Now Book Mark Article - Tall, thin build
Exams and Tests
The health care provider may notice that the child is tall and thin.
Other signs include:
- Curved spine (scoliosis)
Scoliosis
Scoliosis is an abnormal curving of the spine. Your spine is your backbone. It runs straight down your back. Everyone's spine naturally curves a b...
Read Article Now Book Mark Article - Deformity of the chest
- Dislocated lens of the eye
If there is poor or double vision, an eye doctor (ophthalmologist) will perform a dilated eye exam to look for dislocation of the lens or nearsightedness.
There may be a history of blood clots. Intellectual disability or mental illness is also possible.
Tests that may be ordered include any of the following:
- Amino acid screen of blood and urine
- Genetic testing
- Homocysteine level
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Liver biopsy and enzyme assay
Liver biopsy
A liver biopsy is a test that takes a sample of tissue from the liver for examination.
Read Article Now Book Mark ArticleEnzyme assay
ELISA stands for enzyme-linked immunoassay. It is a commonly used laboratory test to detect antibodies in the blood. An antibody is a protein produ...
Read Article Now Book Mark Article - Skeletal x-ray
x-ray
X-rays are a type of electromagnetic radiation, just like visible light. An x-ray machine sends individual x-ray waves through the body. The images...
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Skin biopsy with a fibroblast culture
Skin biopsy
A skin lesion biopsy is when a small amount of skin is removed so it can be examined under a microscope. The skin is tested to look for skin conditi...
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Standard ophthalmic exam
Standard ophthalmic exam
A standard eye exam is a series of tests done to check your vision and the health of your eyes.
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Treatment
There is no cure for homocystinuria. About half of people with the disease respond to vitamin B6 (also known as pyridoxine).
Vitamin B6
Vitamin B6 is a water-soluble vitamin. Water-soluble vitamins dissolve in water so the body cannot store them. Leftover amounts of the vitamin leav...
Read Article Now Book Mark ArticleThose who do respond will need to take vitamin B6, B9 (folate), and B12 supplements for the rest of their lives. Those who do not respond to supplements will need to eat a low-methionine diet. Most will need to be treated with trimethylglycine (a medicine also known as betaine).
Neither a low-methionine diet nor medicine will improve existing intellectual disability. Medicine and diet should be closely monitored by a doctor who has experience treating homocystinuria.
Support Groups
More information and support for people with homocystinuria and their families can be found at:
- National Organization for Rare Disorders -- rarediseases.org/rare-diseases/homocystinuria-due-to-cystathionine-beta-synthase-deficiency/
- HCU Network America -- hcunetworkamerica.org
Outlook (Prognosis)
Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition.
If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns.
People whose blood homocysteine levels continue to rise are at increased risk for blood clots. Clots can cause serious medical problems and shorten lifespan.
Possible Complications
Most serious complications occur due to blood clots. These episodes can be life threatening.
Dislocated lenses of the eyes can seriously damage vision. Lens replacement surgery may be needed.
Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.
When to Contact a Medical Professional
Contact your provider if you or a family member shows symptoms of this disorder, especially if you have a family history of homocystinuria.
Prevention
Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).
If there are known gene conditions in the parents or family, samples from chorionic villus sampling or amniocentesis can be used to test for these defects before a baby is born.
Chorionic villus sampling
Chorionic villus sampling (CVS) is a test some pregnant women have to screen their baby for genetic problems.
Read Article Now Book Mark ArticleAmniocentesis
Amniocentesis is a test that can be done during pregnancy to look for certain problems in the developing baby. These problems include:Birth defectsG...
Read Article Now Book Mark ArticleReferences
Schiff M, Blom HJ. Homocystinuria and hyperhomocysteinemia. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 193.
Shchelochkov OA, Venditti CP. Methionine./Defects in metabolism of amino acids. In: Kliegman RM, St. Geme JW, Blum NJ, et al, eds. Nelson Textbook of Pediatrics. 22nd ed. Philadelphia, PA: Elsevier; 2025:chap 105.1.
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Pectus excavatum - illustration
Pectus excavatum is a condition in which the breast bone (sternum) appears sunken and the chest concave. It is sometimes called funnel chest. The majority of these cases are not associated with any other condition (isolated findings). However, some genetic conditions include pectus excavatum.
Pectus excavatum
illustration
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Pectus excavatum - illustration
Pectus excavatum is a condition in which the breast bone (sternum) appears sunken and the chest concave. It is sometimes called funnel chest. The majority of these cases are not associated with any other condition (isolated findings). However, some genetic conditions include pectus excavatum.
Pectus excavatum
illustration
Review Date: 12/31/2023
Reviewed By: Anna C. Edens Hurst, MD, MS, Associate Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.