Classical homocystinuria (NORD)
Definitions & Key takeaways
Classical homocystinuria, also known as Cystathionine Beta-Synthase (CBS), is a genetic disorder caused by a mutation of the CBS gene, resulting in impaired homocysteine metabolism. Homocysteine is a compound that is derived from the amino acid methionine. Normally, the CBS enzyme helps to break down a protein called homocysteine. When it is not working properly, homocysteine levels can become very high. This can damage blood vessels and organs, including the heart, brain, and eyes.
Symptoms include poor growth and developmental delay in infants, myopia, and downward and inward subluxation of the eye lens. Also, people with classical homocystinuria often have a tall, thin build and long limbs. They may also have a small head size, scoliosis, and osteoporosis. Intellectual disability is common in this disorder. High levels of homocysteine can damage the blood vessels, leading to problems with the heart, brain, and eyes. For example, people with this disorder may have an increased risk of stroke or other problems with the blood vessels in the brain. They may also have an increased risk for cataracts or other issues with the eyes.
Classical homocystinuria also called cystathionine beta synthase or CBS deficiency is characterized by too much of the amino acid homocysteine in the blood and urine amino acids are the building blocks of proteins and proteins are needed for proper growth and development of our bodies.
Enzymes are a type of protein in the body which helps speed up chemical reactions. CBS deficiency usually occurs when there is a problem with one of the enzymes involved in converting the amino acid methionine into the amino acid cysteine, resulting in a buildup of methionine and homocysteine and decreased production of cystine.
This buildup of methionine and homocysteine amino acids can cause a wide range of symptoms which vary by severity and age infants experience generalized symptoms such as slow growth and weight gain as well as possible developmental delays.
After age three, more specific symptoms begin to appear. Symptoms in the eyes may include the lenses of the eye dislocating or becoming cloudy, severe nearsightedness and quivering of the iris.
Other symptoms may include vision loss from damage to the primary nerve that sends signals from the eye to the brain, severe headache or eye pain from increased pressure in the back of the eye and blurry vision or floaters in the field of vision from retinal damage.
Skeletal abnormalities also occur with people affected by the condition characteristically, having long lanky limbs and knees that bend towards each other.
When standing up straight, the arch of the inside of the foot may be high with the majority of the foot not touching the ground.
The chest may also stick out more than usual or cave inward. Older individuals with CBS deficiency tend to experience a decrease in bone density, making it easier for their bones to fracture.
Blood clots can also form at any age causing the most serious complications of CBS deficiency depending on the location of the clot.
These complications include strokes from clots in the brain and pulmonary embolism from blood clots in the lungs. Individuals with classical homocystinuria may also have intellectual disability or experience mental health conditions such as anxiety, depression and obsessive compulsive disorder.
Classical homocystinuria is caused by mutations in the CBS gene and follows autosomal recessive inheritance. An individual must inherit a copy of the mutated CBS gene from both parents to be affected by the disorder.
A mutated CBS gene decreases activity of the enzyme, cystathionine, beta synthase or CBS without a properly functioning CBS.
Enzyme methionine can not easily be converted to cystine causing methionine and homocysteine to increase in the body. While cystine levels remain low altered concentrations of these amino acids can interfere with the stability of important proteins in the skin's connective tissue and other proteins in the body.
Leading to problems such as skeletal abnormalities and blood clots. Classical homocystinuria is diagnosed through a clinical examination, which includes taking a patient history, evaluating signs and symptoms and a physical exam.
If homocystinuria is suspected, a variety of specialized tests will be conducted including blood and urine tests for homocysteine, methionine and cystine levels and genetic testing for changes in the CBS gene.
More severe forms of classical homocystinuria can be diagnosed in a newborn screening by testing for elevated methionine levels.
Treatment focuses on reducing symptoms by regulating the amount of homocysteine in blood plasma. The first treatment used to control homocysteine levels is supplemental B6 or pyridoxine.
Vitamin B6 assists in conversion of homocysteine to cystine. So increased B6 may lower homocysteine levels.
Individuals who do not get better with supplemental B6 alone may require an oral medication called betaine, which helps to break down homocysteine.
If symptoms persist, dietary changes might be suggested to minimize consumption of proteins and methionine by limiting animal proteins such as bacon and eggs and replacing them with more plant based proteins like beans, special metabolic foods and formulas may be required to prevent homocysteine levels from becoming too high since many foods have methionine and protein.
Additional supplements may be recommended including vitamins B nine and B12 and less commonly cystine. Other symptoms may be treated as appropriate.
Genetic counseling is recommended to help families understand the genetics and natural history of homocystinuria and to provide psychosocial support.
All right, as a quick recap classical homocystinuria also called cystathionine beta synthase deficiency causes increased homocysteine levels.
In blood plasma. And urine symptoms vary significantly and often cause eye problems such as nearsightedness and in severe forms can cause blood clots leading to stroke.
CBS is caused by mutations in a gene which regulates cystathionine beta synthase diagnosis includes a clinical examination, followed by specific blood plasma and urine tests.
The primary treatment is vitamin b6, but other treatments such as betaine and a low protein diet might also be needed.
No notes for this video yet
Try adding a note below