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It is a metabolic disorder of methionine, which leads to an abnormal accumulation of homocysteine and its metabolites in the blood and urine.
Also known as beta-cystathionine deficiency (CBS), it is an autosomal recessive hereditary defect in the transulfurization pathway (homocystinuria I) or methylation pathway (homocystinuria II and III).
Which means that a child needs to inherit a copy of the defective gene from both parents to be affected or can be acquired with a deficiency of B6, B12 or folate.
The term homocystinuria describes a greater excretion of homocysteine from the amino acid thiol in the urine. The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency.
symptom
The signs and symptoms of homocystinuria usually develop during the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.
The most common form of homocystinuria is characterized by myopia, lens dislocation in the front of the eye, increased risk of abnormal blood clots, and fragile bones that are prone to fractures ( osteoporosis ) or other skeletal abnormalities.
Less common forms of homocystinuria can cause intellectual disability, lack of growth and weight gain at the expected rate, seizures, movement problems and a blood disorder called megaloblastic anemia .
Megaloblastic anemia occurs when a person has a low number of red blood cells(anemia) and the remaining red blood cells are larger than normal (megaloblastic).
Other signs and symptoms of homocystinuria that can be seen include the following:
- Redness of the cheeks
- Particular musculoskeletal characteristics such as: Tall and thin structure, long limbs, arched feet.
- Psychiatric diseases.
- Eye abnormalities such as ectopia lentis, glaucoma , optic atrophy, retinal detachment and cataracts.
- Vascular disease
- Extensive atheroma formation at an early age that affects many arteries but not the coronary arteries.
- Trombosis intravascular.
Causes
It is caused by the deficiency of the enzyme cystathionine beta synthase or the deficiency of folic acid, vitamin B12 and pyridoxine (vitamin B6), or mutations of related enzymes.
Diagnosis
The diagnosis is obtained by routine metabolic biochemistry. Amino acid tests are performed in the blood and urine that show the high concentration of homocysteine and methionine and the low concentration of cysteine.
The multisystem connective tissue disorder, the muscles, the central nervous system and the cardiovascular system may be a consequence of homocystinuria
Treatment
Many patients are treated with high doses of vitamin B6 (also known as pyridoxine) and less than 50% respond to this treatment and need to take vitamin B6 supplements for the rest of their lives. Those who do not respond require a diet low in sulfur and most will need treatment with trimethylglycine.
A normal dose of folic acid supplement and, occasionally, the addition of cysteine to the diet may be useful, since glutathione is synthesized from cysteine (so the addition of cysteine may be important to reduce oxidative stress ).
To reduce homocysteine concentrations and promote the conversion of homocysteine to methionine, betaine is administered. This increases the flow through the remethylation pathway independent of the folate derivatives (which is active primarily in the kidneys and the liver).
Recommended diet:
Low protein food is recommended for this disorder, which requires low food products in particular types of amino acids (eg, methionine).
Forecast
The life expectancy of patients with homocystinuria is reduced only if they do not receive treatment. It is known that before the age of 30 years, almost a quarter of patients die as a result of thrombotic complications (for example, heart attack ).
