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 help 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 cysteine.
This build up 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 cannot easily be converted to cysteine causing methionine and homocysteine to increase in the body while cysteine levels remain low.