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Disease Profile


Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable



Homocystinuria refers to a group of inherited disorders in which the body is unable to process certain building blocks of proteins (amino acids) properly. This leads to increased amounts of homocysteine and other amnio acids in the blood and urine. The most common type of genetic homocystinuria, called CBS deficiency, is caused by the lack of an enzyme known as cystathionine beta-synthase (CBS). Most states in the United States test for homocystinuria due to CBS deficiency at birth by newborn screening. Other types are less common, and are caused by different missing or non-working enzymes. Homocystinuria can affect the eyes, skeleton, central nervous system and the blood clotting system. Mutations in the MTHFR, MTR, MTRR and MMADHC genes can cause homocystinuria. All these forms of homocystinuria are inherited in an autosomal recessive manner.[1] Treatment and long-term outlook varies depending upon the cause of the disorder.


Symptoms of the most severe form of homocystinuria will start in infancy or early childhood. he first of these symptoms may be poor growth and failure to gain weight.[1][2][3] Other people with homocystinuria may not have any symptoms until adulthood. The most common symptom seen in adults with homocystinuria is an abnormal blood clot.[3]

Other symptoms of untreated homocystinuria can include:

Dislocation of the lens of the eye

Caved-in chest (pectus excavatum)
Curvature of the spine (scoliosis)
Long, thin bones
Osteoporosis (weak, brittle bones)

Central nervous system
Learning and intellectual disabilities
Psychiatric problems

Blood and heart: 
Cardiovascular disease
Abnormal blood clots 


Homocystinuria can be caused by mutations in several different genes. All of these genes are responsible for making enzymes that are involved in the way our body uses and processes amino acids. The most common gene associated with homocystinuria is the CBS gene that causes a lack of the enzyme, cystathionine beta-synthase. Rarer causes of homocystinuria include mutations in the MTHFR, MTR, MTRR and MMADHC genes.[1] It is not clear why high levels of homocysteine cause the symptoms seen in homocystinuria.

There are other, non-genetic causes of high levels of homocysteine.[4] Non-genetic homocystinuria is not a rare condition. Some of the non-genetic causes are listed here.

Vitamin B6 or vitamin B12 deficiency
Folate deficiency 
Low thyroid hormones (hypothyroidism)
High cholesterol
Physical inactivity
High blood pressure
Certain medications (such as carbamazepine, atorvastatin, fenofibrate, methotrexate, phenytoin, and nicotinic acid)
Advanced age


Most states in the US test for homocystinuria due to CBS deficiency at birth by newborn screening. A baby that has a positive newborn screening test needs to have additional blood testing to look for high levels of homocysteine and methionine in the blood. Genetic testing can also be helpful for diagnosis.[1][2]

A child or an adult with dislocation of the lens of the eye may also get tested for homocystinuria using blood and urine testing. In addition, a child or adult who has a blood clot, especially at an early age, may also get tested for homocystinuria. 

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.


    People who have the most severe form of homocystinuria are put on a special protein-restricted diet to reduce the blood levels of homocysteine and methionine. In addition, they may be given supplements including vitamin B6, vitamin B12, folate and betaine. The recommendation is that these people stay on the protein-restricted diet for life. People with milder forms may be treated with supplements depending on the level of homocysteine in their blood.[3][5]

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Homocystinuria. This website is maintained by the National Library of Medicine.
      • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
      • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Homocystinuria. Click on the link to view a sample search on this topic.


          1. Homocystinuria. Genetics Home Reference (GHR). March, 2016; https://ghr.nlm.nih.gov/condition=homocystinuria.
          2. Homocystinuria. Screening, Technology and Research in Genetics (STAR-G). Updated 2/18/2016; https://www.newbornscreening.info/Parents/aminoaciddisorders/CBS.html.
          3. Morris AA, Kozich V, Santra S et al. Guidelines for the diagnosis and treatment of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017; 40(1):49-74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203861/pdf.
          4. Varga E and Moll S. Homocysteine and MTHFR Mutations. Circulation. 2015; 132:e6-e9. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.114.013311.
          5. Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H. Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options. Biochem Genet. Apr 2018; 56(1-2):7-21. https://www.ncbi.nlm.nih.gov/pubmed/29094226.

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