Гомоцистинурия: причины, симптомы и методы лечения.

Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. Flush across the cheeks
Musculoskeletal
Tall, thin build resembling Marfanoid habitus or subluxation of lens
Myopia (nearsightedness)
Glaucoma
Optic atrophy
Retinal detachment
Cataracts
Vascular disease
Homocysteine binds to the endothelium of the blood vessels and activate signaling pathways leading to the release of pro inflammatory molecules. This may cause the following :
Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries
Intravascular thrombosis

It is usually caused by the deficiency of the enzyme cystathionine beta synthase, Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis. The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e. g., cysteine in cystine homocysteine, homocysteine in homocysteine homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocysteine is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.

No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B6 for the rest of their lives. Those who do not respond require a Low sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress). Riboflavin, a cofactor for the MTHFR enzyme pathway and multiple glutathione related pathways, may also be used. Betaine (N,N,N trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i. e., increasing flux through the re methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys). The re formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S adenosyl methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.

Low protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e. g., methionine).

The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e. g., heart attack).

One theory suggests that Akhenaten, a pharaoh of the eighteenth dynasty of Egypt, may have had homocystinuria.