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.

So what happens when you have High homocysteine levels, it may mean you may have a vitamin
deficiency.

So what does CBS do? CBS gene provides instructions for making an enzyme called cystathionine beta-
synthase and we all know that enzymes are a type of protein in the body which helps speed up chemical
reactions. So This enzyme acts in a chemical pathway and is responsible for using vitamin B6 to convert
the amino acid called homocysteine and serine to a molecule called cystathionine.

We are familiar with the word amino acids so, Amino acids are the building blocks of proteins, and
proteins are needed for the proper growth and development of our bodies.

Mutations in the CBS gene disrupt the function of cystathionine beta-synthase, preventing
homocysteine from being used properly. As a result, this amino acid and toxic byproducts substances
build up in the blood.

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 build-up of methionine and
homocysteine and decreased production of cysteine.

Homocysteine- Homocysteine is a type of amino acid, a chemical your body uses to make proteins.
Normally, vitamin B12, vitamin B6, and folic acid break down homocysteine and change it into other
substances your body needs. There should be very little homocysteine left in the bloodstream because
large amounts can have toxic effects through a handful of general possible mechanisms.

Methionine- Methionine is a unique sulfur-containing amino acid that can be used to build proteins and
produce many molecules in the body. These include the antioxidant glutathione and the molecule SAM
(S-adenosylmethionine) which is used to modify DNA and other molecules.

Cysteine- Cysteine is a non-essential amino acid important for making protein, and for other metabolic
functions. It's found in beta-keratin. This is the main protein in nails, skin, and hair. Cysteine is important
for making collagen. Cysteine stabilizes the tridimensional structure of proteins, which is critical for
extracellular proteins that might be exposed to harsh conditions. Proteins containing multiple disulfide
bridges are more resistant to eg, thermal denaturation, and thus may maintain their biological activity
under more extreme conditions.

Symptoms

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 in people affected by this kind of 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.

Cause

Classic 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 the 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. Altered
concentrations of these amino acids can interfere with the stability of important proteins in the skin,
connective tissue and other proteins in the body, leading to problem such as skeletal abnormalities and
blood clots.

Diagnosis

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
cysteine 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

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 cysteine, so increased B 6 may lower homocysteine levels.
Individuals who do not get better with supplemental B Six alone may require a normal 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
B9 and B12, and less commonly, cysteine. 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.
Recap

Alright as a quick recap.

Classical homocystinuria, also called cystathionine beta-synthase deficiency, causes increased