Rare Nephrology News

Disease Profile

Homocystinuria due to CBS deficiency

Prevalence
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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

E72.1

Inheritance

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

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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

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X-linked
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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

Homocystinuria due to cystathionine beta-synthase deficiency; Cystathionine beta-synthase deficiency; CBS deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Homocystinuria due to CBS deficiency is an inherited disorder in which the body is unable to correctly use the amino acid, homocysteine, one of the building blocks of protein.[1][2][3] This form of homocystinuria is caused by a genetic mutation in the CBS gene, which leads to low levels or absence of an enzyme called cystathionine beta-synthase (CBS).[1][2][3] When CBS is absent or not working right, homocysteine and other toxic chemicals build up in the blood and urine. Symptoms of this disorder include poor growth and slow weight gain in infancy. Additional symptoms include nearsightedness, dislocation of the lens of the eye, an increased risk of blood clots, and developmental problems.[1] Homocystinuria due to CBS deficiency is inherited in an autosomal recessive pattern.[1] It is diagnosed by newborn screening, or later in life by blood and urine testing. There are two types of homocystinuria due to CBS deficiency. One type responds to treatment with vitamin B6 and the other one does not. Other treatments for this disorder include a protein-restricted diet, betaine treatment, and other supplements. With early treatment, individuals with this condition can have normal growth and development.[1][3]

Symptoms

The symptoms of homocystinuria due to CBS deficiency can vary from person to person. In infancy, symptoms include poor weight gain and growth, as well as problems with development.[1][2][3] If untreated, additional symptoms can develop that include:

  • Nearsightedness
  • Dislocation of the lens of the eye
  • Skeletal abnormalities
  • Osteoporosis
  • Blood clots
  • Seizures
  • Intellectual disability
  • Psychiatric issues

The symptoms of the vitamin B6 responsive form of homocystinuria are generally milder than those of the non-responsive form.[2][3] Some people with homocystinuria do not develop symptoms until adulthood. One of the only symptoms in adults with homocystinuria may be blood clots.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of amino acid metabolism
0004337
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Dental crowding
Crowded teeth
Dental overcrowding
Overcrowding of teeth

[ more ]

0000678
Disproportionate tall stature
0001519
Ectopia lentis
0001083
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Osteoporosis
0000939
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
30%-79% of people have these symptoms
Amblyopia
Lazy eye
Wandering eye

[ more ]

0000646
Arterial thrombosis
Blood clot in artery
0004420
Arteriovenous malformation
0100026
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Genu valgum
Knock knees
0002857
Hypertension
0000822
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Kyphosis
Hunched back
Round back

[ more ]

0002808
Myopia
Close sighted
Near sightedness
Near sighted
Nearsightedness

[ more ]

0000545
Pectus carinatum
Pigeon chest
0000768
Pectus excavatum
Funnel chest
0000767
Pulmonary embolism
Blood clot in artery of lung
0002204
Scoliosis
0002650
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

0002209
Venous thrombosis
Blood clot in vein
0004936
5%-29% of people have these symptoms
Abnormality of retinal pigmentation
0007703
Anorexia
0002039
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Elevated hepatic transaminase
High liver enzymes
0002910
Esophageal varix
Enlarged vein in esophagus
0002040
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Glaucoma
0000501
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hepatomegaly
Enlarged liver
0002240
Hernia
0100790
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Intracranial hemorrhage
Bleeding within the skull
0002170
Optic atrophy
0000648
Psychosis
0000709
Retinal detachment
Detached retina
0000541
Seizure
0001250
Subcutaneous hemorrhage
Bleeding below the skin
0001933
Urticaria
Hives
0001025
1%-4% of people have these symptoms
Lens subluxation
Partially dislocated lens
0001132
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Biconcave vertebral bodies
0004586
Brittle hair
0002299
Cutis marmorata
0000965
Depressivity
Depression
0000716
Generalized osteoporosis
0040160
Global developmental delay
0001263
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Homocystinuria
High urine homocystine levels
0002156
Hyperhomocystinemia
Elevated blood homocystine
0002160
Hypermethioninemia
Increased methionine in blood
0003235
Hypopigmentation of the skin
Patchy lightened skin
0001010
Inguinal hernia
0000023

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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.
    • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are 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.
    • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
    • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

      Treatment

      People with homocystinuria due to CBS deficiency who do not respond to vitamin B6 are treated with a special, protein-restricted diet to help lower the amount of methionine and homocysteine in their bodies. In addition, they may be given supplements, such as vitamin B12, folate, and betaine. Specially trained nutritionists and dieticians work with patients to adjust the diet and protein requirements as needed. To avoid the complications seen with CBS deficiency, people with this disorder need to remain on a special diet for life.[4]

      People with the vitamin B6 responsive form of this disorder are treated with vitamin B6. In some people, diet restrictions are necessary as well.[4]

      Management Guidelines

      • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

        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.

        Organizations

        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

          • Genetics Home Reference (GHR) contains information on Homocystinuria due to CBS deficiency. This website is maintained by the National Library of Medicine.
          • 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

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • 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.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Homocystinuria due to CBS deficiency. Click on the link to view a sample search on this topic.

              References

              1. Homocystinuria. Genetics Home Reference (GHR). March, 2016; https://ghr.nlm.nih.gov/condition=homocystinuria.
              2. Sacharow S, Picker JD, Levy HL. Homocystinuria Cuased by Cystathionine Beta-Synthase Deficiency. GeneReviews. 2017; https://www.ncbi.nlm.nih.gov/books/NBK1524.
              3. Homocystinuria due to cystathionine beta-synthase deficiency. National Organization for Rare Disorders (NORD). 2018; https://rarediseases.org/rare-diseases/homocystinuria-due-to-cystathionine-beta-synthase-deficiency.
              4. 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.
              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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