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This is a clinical test intended for Help: Diagnosis, Mutation Confirmation

Clinical summary


Imported from GeneReviews

Homocystinuria caused by cystathionine β-synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scolioisis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four ‒ or only one ‒ of the systems can be involved; expressivity is variable for all of the clinical signs. It is not unusual for a previously asymptomatic individual to present in adult years with only a thromboembolic event that is often cerebrovascular. Two phenotypic variants are recognized, B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive homocystinuria is usually milder than the non-responsive variant. Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.

Clinical features


Imported from Human Phenotype Ontology (HPO)

  • Arachnodactyly
  • Depression
  • Ectopia lentis
  • Glaucoma
  • Inguinal hernia
  • Homocystinuria
  • Lens subluxation
  • Mitral valve prolapse
  • Myocardial infarction
  • Myopia
  • Osteoporosis
  • Pancreatitis
  • Personality disorder
  • Scoliosis
  • Seizure
  • Stroke
  • Thromboembolism
  • Dental crowding
  • Pectus carinatum
  • Hypopigmentation of the skin
  • Atypical behavior
  • High palate
  • Tall stature
  • Cutis marmorata
  • Brittle hair
  • Global developmental delay
  • Kyphoscoliosis
  • Disproportionate tall stature
  • Biconcave vertebral bodies
  • Methioninuria
  • Limitation of joint mobility
  • Pectus excavatum
  • Failure to thrive
  • Hepatic steatosis
  • Visual impairment
  • Intellectual disability
  • Hyperhomocystinemia
  • Hypermethioninemia
  • Generalized osteoporosis
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Inheritance pattern


Autosomal recessive inheritance

Conditions tested

Target population


Individuals whose clinical findings are consistent with the specific disorder.


Not provided

Clinical validity


Not provided

Clinical utility


Not provided

Practice guidelines

  • ACMG ACT, 2021
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Methionine +/- Elevated Homocysteine, Homocystinuria (Cystathionine beta-synthase deficiency), 2021
  • ACMG Algorithm, 2021
    American College of Medical Genetics and Genomics, Algorithm, Elevated Methionine +/- Elevated Homocysteine, 2021
  • ACMG ACT, 2012
    American College of Medical Genetics and Genomics, Transition to Adult Health Care ACT Sheet, Homocystinuria (CBS Deficiency), 2012

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