Homocystinuria

What is the cause of homocystinuria?

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. 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. 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)
• Obesity
• Diabetes
• High cholesterol
• Physical inactivity
• High blood pressure
• Certain medications (such as carbamazepine, atorvastatin, fenofibrate, methotrexate, phenytoin, and nicotinic acid)
• Smoking
• Advanced age

Last updated on 05-01-20

How is homocystinuria diagnosed?

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.

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.

Last updated on 05-01-20

How is homocystinuria inherited in families?

The genetic forms of homocystinuria are inherited in an autosomal recessive pattern, which means both copies of the gene in every cell have mutations. This means that to have the condition, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this.

People with homocystinuria inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to have the condition
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

Last updated on 05-01-20

What is known about homocystinuria and pregnancy?

Pregnancy increases the risk for blood clots, stroke, and heart disease in women with homocystinuria, especially in the post-partum period. Most pregnancies, however, are uncomplicated. Prophylactic anticoagulation (preventing blood clots) during the third trimester of pregnancy and post partum in women with homocystinuria is recommended to reduce risk of thromboembolism.Women are often given blood thinning medication (such as herapin) during the last few months of pregnancy until about 6 weeks after delivery. Aspirin in low doses has also been given throughout pregnancy. The usual treatments for homocystinuria are typically continued during pregnancy. In addition to blood clots, untreated women are at higher risk for miscarriage and stillbirth.

Maternal homocystinuria does not appear to have major teratogenic effects (effects that can harm the development of the embryo or fetus) requiring additional counseling or, with respect to the fetus, more stringent management. Nevertheless, treatment with pyridoxine or methionine-restricted diet or both should be continued during pregnancy. Betaine may also be continued and appears not to be teratogenic.

A 2002 study in the Journal of Inherited Metabolic Disease obtained information on 11 women with maternal homocystinuria, their pregnancies (15 total), and their offspring. 5 women were pyridoxine-nonresponsive and 6 were pyridoxine-responsive. The authors reported there was no relationship between the severity of the homocystinuria or the therapies during pregnancy to either the pregnancy complications or the offspring outcomes. They stated that the infrequent occurrences of pregnancy complications, offspring abnormalities and maternal thromboembolic events in the series suggest that pregnancy and outcome in maternal homocystinuria are usually normal. Nevertheless, a cautious approach would include careful monitoring of these pregnancies with attention to metabolic therapy and possibly anticoagulation.

Last updated on 05-01-20

What is the long-term outlook for people with homocystinuria?

Lowering the level of homocysteine in the blood, either with diet or supplements or both, can prevent symptoms. With treatment, people with the most severe form of homocystinuria can have normal growth and development. Some may still have eye problems or blood clots and should be monitored. Blood clots can be serious and cause organ damage.

Treatment for milder forms of homocystinuria may depend on clinical symptoms and the level of homocysteine in the blood.

Last updated on 05-01-20

How many people have homocystinuria?

Approximately 1 in 200,000 to 1 in 300,000 people in the US has the most common type of homocystinuria (homocystinuria due to CBS deficiency). In other countries, the prevalence is higher. In Quatar, about 1 in 1,800 people has this disorder and in Norway, about 1 in 6,400 people has it. World-wide, it is thought that about 1 in 150,000 people has homocystinuria due to either a CBS or an MTHFR gene mutation. It is unclear how many people have homocystinuria due to other gene mutations.

Last updated on 05-01-20

How might homocystinuria be treated?

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.

Last updated on 05-01-20

Name: Metabolic Support UK 5 Hilliards Court Sandpiper Way
Chester Business Park
Chester, CH4 9QP, United Kingdom
Phone: 0845 241 2173 Toll Free: 0800 652 3181 Email: https://www.metabolicsupportuk.org/contact-us Url: https://www.metabolicsupportuk.org
Name: Genetic Metabolic Dietitians International P.O. Box 1462
Hillsborough, NC, 27278, United States
Email: info@gdmi.org Url: http://www.gmdi.org/
Name: HCU Network America 623 Creek Lane
Flourtown, PA, 19031, United States
Phone: 630-360-2087 Email: info@hcunetworkamerica.org Url: http://hcunetworkamerica.org/
Homocystinuria Genetics Home Reference. March 2016; Reference Link Varga E and Moll S. Homocysteine and MTHFR Mutations Circulation. 2015; 132. e6-e9. Reference Link

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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