Other Names

Classic homocystinuria


Cystathionine beta-synthase deficiency (CBS)

Diagnosis Coding

E72.11, homocystinuria

Disorder Category

An amino acidemia



Elevated methionine

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA


A deficiency of cystathionine beta-synthase (CBS) results in the inability to degrade homocystine to cystathionine, resulting in increased levels of homocysteine and methionine. A variant that represents a minority of cases is responsive to vitamin B6 (pyridoxine), but this type may be missed by newborn screening. Elevated homocysteine impairs the function of several proteins (including fibrillin) interfering with the formation of disulfide bonds and impairs endothelial function, leading to thrombosis.


About 1:200,000 - 1:300,000 live births, as high as 1:65,000 in Ireland [Homocystinuria - Information for Professionals (STAR-G) Homocystinuria (GeneReviews)


Autosomal recessive

Prenatal Testing

DNA testing by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme assay possible by amniocentesis.

Clinical Characteristics

With treatment normal IQ is possible and reduction of thromboembolic events may decrease the incidence of other sequelae, such as ectopia lentis, seizures, and psychiatric problems. Without treatment, symptoms vary widely and may present at different ages, ranging from lens dislocation, poor vision, developmental delays, marfanoid habitus, and acute thromboembolism.

Initial symptoms in infants and toddlers may include:
  • Developmental delay
  • Emotional and behavior problems
  • Thromboembolism
  • Ectopia lentis (dislocation of the ocular lens) or severe myopia (nearsightedness)
Findings in older children and adults may include:
  • Marfanoid habitus: tall/ thin build; long fingers, arms, and legs
  • Genu valgum, pes cavus
  • Osteoporosis
  • Malar flush
  • Decreased hair, skin, iris pigmentation
  • Seizures
  • Vascular disease and stroke
  • Psychiatric abnormalities
  • Mental retardation

Follow-up Testing after Positive Screen

Quantitative plasma amino acid analysis, total plasma homocysteine.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Homocystinuria - Information for Parents (STAR-G)).
  • Assist in implementation and maintenance of a diet low in methionine and proteins; baby aspirin is also recommended starting in late teenager years.
  • Provision of vitamin B6, betaine, vitamin B12, and methylfolate may be indicated.
  • Regular blood and urine tests to monitor amino acid levels and diet may be indicated.
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation with the following service(s): Pediatric Genetics (see NV providers [5]) and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Homocystinuria (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Disease InfoSearch for Homocystinuria (Genetic Alliance)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more.

Homocystinuria (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; American Academy of Pediatrics.

For Parents and Patients

Homocystinuria - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

Homocystinuria (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.


ACT Sheet for Homocystinuria (ACMG)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Services for Patients & Families in Nevada (NV)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Helpful Articles

PubMed search for homocystinuria and neonatal screening, last 5 years.

Mudd SH.
Hypermethioninemias of genetic and non-genetic origin: A review.
Am J Med Genet C Semin Med Genet. 2011;157(1):3-32. PubMed abstract
Discusses briefly the genetic and non-genetic conditions that sometimes lead to abnormally elevated methionine. Focuses on recent developments and differential diagnosis of hypermethioninemia.

Authors & Reviewers

Initial publication: March 2007; last update/revision: July 2012
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Reviewer: Kimberly Hart, MS, LCGC