Cystathionine beta-synthase deficiency; CBS deficiency; HCY
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.
Homocystinuria has several features in common with Marfan syndrome, including joint and eye changes.
Newborn infants appear healthy. Early symptoms, if present, are not obvious.
Other symptoms include:
- Chest deformities (pectus carinatum, pectus excavatum)
- Flush across the cheeks
- High arches of the feet
- Intellectual disability
- Knock knees
- Long limbs
- Mental disorders
- Spidery fingers (arachnodactyly)
- 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)
- 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
- Liver biopsy and enzyme assay
- Skeletal x-ray
- Skin biopsy with a fibroblast culture
- Standard ophthalmic exam
There is no cure for homocystinuria. About half of people with the disease respond to vitamin B6 (also known as pyridoxine).
Those 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 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 supervised by a doctor who has experience treating homocystinuria.
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.
Most serious complications result from 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 consequence of the disease. But, it can be reduced if diagnosed early.
When to Contact a Medical Professional
Call your provider if you or a family member shows symptoms of this disorder, especially if you have a family history of homocystinuria.
Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Intrauterine 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 defect in the parents or family, samples from chorionic villus sampling or amniocentesis can be used to test for these defects.
Rezvani I, Melvin JJ. Defects in metabolism of amino acids. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2015:chap 85.3.
Rezvani I, Melvin JJ. Picker JD, Levy HL. Homocystinuria caused by cystathionine beta-synthase deficiency. GeneReviews. Seattle, WA: University of Washington; 2014:11. PMID: 20301697 www.ncbi.nlm.nih.gov/pubmed/20301697.
Schiff M, Blom H. Homocystinuria and hyperhomocysteinemia. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 209.
Reviewed By: Chad Haldeman-Englert, MD, FACMG, Fullerton Genetics Center, Asheville, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.