Homocystinuria: Symptoms and Treatment

Homocystinuria is a genetic disorder associated with a metabolic disorder in the amino acid methionine. It is rare. In this case, the nervous system is affected, eyesight, osteoarticular apparatus is affected, multiple thromboses of blood vessels are formed. For diagnosis, molecular genetic methods, biochemical methods of blood and urine tests are used. Treatment is based on the exclusion of food products containing methionine, and the intake of vitamin B6. In some cases, medicines are additionally used. From this article you can get basic information about homocystinuria, about the symptoms and treatment of this disease.

Causes

The amino acid methionine enters the human body with food. It is an indispensable amino acid, that is, it can not be synthesized from other substances. With the normal functioning of biochemical processes from methionine, a number of transformations form cystathionine and cystine. Intermediate product of similar reactions is homocysteine. To implement the whole cascade of transformations, a number of enzymes are needed, the work of some of them depends on the intake of folic acid, vitamin B6 and B12 into the body.

At the heart of homocystinuria is the insufficiency of the enzyme cystathione synthetase, which results in the accumulation of homocysteine ​​and methionine in the human body. Deficiency of the vitamin B6, B12 and folic acid content can help reduce the activity of the enzyme. Accumulation of homocystine and methionine is accompanied by a toxic effect on the nervous, connective tissue (destroys the structure of collagen), leads to an increase in the coagulation properties of blood and education thrombi.

The concentration of the cystathione synthetase enzyme is determined by the normal functioning of the gene located in the 21st chromosome. If the mutation affects this chromosome, then homocystinuria occurs.

There are two types of the disease:

• B6-dependent (pyridoxine-sensitive): with it the concentration of cystathione synthetase is normal, but the activity of the enzyme is reduced. Treatment with high doses of vitamin B6 improves a person's condition;
• B6-independent (pyridoxine-resistant): the intake of vitamin B6 does not normalize the function of the enzyme.

The disease is transmitted by an autosomal recessive type of inheritance. This means that it does not depend on sex (it affects both men and women), and the appearance of clinical signs is possible when the mutant genes coincide in the child from the mother and father. That is, once arose mutation is transmitted from generation to generation imperceptibly (when there is one "wrong" gene, there are no symptoms of the disease) until the mutant genes coincide. The disease is rare: 1 case per 200 000 population.

Symptoms

In children with homocysteinuria, abnormalities of the musculoskeletal system are often detected.

The disease is very polymorphic, that is, the emerging symptoms indicate the defeat of various organs and systems.

Newborn babies are no different from healthy babies. Then the children begin to eat, methionine enters the body, its metabolism is disturbed, and the accumulation of toxic substances begins. All the symptoms appear gradually as the concentration of methionine and homocystine in the blood and urine increase.

The main clinical symptomatology develops in the first 10 years of life.

All manifestations of homocystinuria can be represented as follows:

• the child has a lag in the set of body weight and height. The introduction of corrective additives and lures only aggravates the process;
• characteristic irritability, tearfulness, sleep disturbance, mental retardation;
• late closure of the fontanelles;
• the defeat of the eye is very specific for homocystinuria subluxation of the lens, as well as a sharp decreased visual acuity (pronounced nearsightedness), trembling of the iris (the color part of the eye around pupil). Gradually formed astigmatism, cataracts, increased intraocular pressure, develops atrophy of the optic nerves and, as a consequence, blindness. Retinal detachment is possible;
• defeat of the musculoskeletal system: anomalies in the structure of the body are revealed. Possible disproportionately long limbs and fingers (arachnodactyly), flat feet or a hollow foot, excessive mobility joints, keel ("chicken" chest) or funnel-shaped chest, curvature of the spine and lower legs, high (gothic) sky. Early development of osteoporosis, in connection with which often there are numerous pathological bone fractures with minor injuries;
• the defeat of the vascular system is associated with multiple thrombosis. Thrombi are formed in both arterial and venous vessels of any localization: in the lungs (thromboembolism pulmonary artery), in the heart (infarcts), in the kidneys, in the limbs (thrombophlebitis), in the brain (strokes);
• defeat of the nervous system: in most cases it is associated with progressive thrombosis of small vessels. It manifests itself as a violation of intellectual development, muscle tone, the appearance of involuntary movements in the limbs, epileptic seizures, mental disorders. The formation of thrombosis in large vessels is fraught with the emergence of ischemic strokes with the development of paresis in the limbs, speech impairment, coordination, swallowing, a violation of sensitivity;
• skin lesion: reddish spots appear in the cheekbones on the face ("burning" cheekbones), on the limbs, telangiectasia (vascular "stars").

There are external features (phenotypic) of patients with homocystinuria: they are tall, thin people with light rare hair and blue eyes (sometimes even albinos).

Diagnostics

To establish the diagnosis, biochemical blood and urine tests are performed: an increased level of methionine, homocystin is determined.

Specific enzymatic defect of cystathione synthetase is determined in the culture of fibroblasts, in biopsies of the skin and liver.

The final diagnosis is made on the basis of data from molecular genetic methods (detection of a mutation).

In families where there are already homocystinuria-infected children, in the event of repeated pregnancies it is necessary to perform prenatal (prenatal) diagnosis in order to exclude the disease in the fetus.

Treatment

Homocystinuria is an incurable disease. But you can learn to live with it. Therapeutic tactics depend on the form of the disease.

Pyridoxine sensitive form is amenable to the use of large doses of vitamin B6 (50-600 mg / day).At the same time, it is recommended to take folic acid 1 mg / day. In such cases it is possible to "force" the enzyme to work normally and to avoid the toxic effects of homocystin and methionine.

Pyridoxine-resistant form is treated with a diet that excludes the entry of methionine into the body. Food is mainly of vegetable origin, containing little protein. Meat, cheese, eggs, cottage cheese, fish, soybeans are excluded from the diet. Allowed products such as goat or mare's milk, women's milk (that is, breastfeeding is encouraged), kefir, corn flakes, rice, potatoes, carrots, beets, cabbage, tomatoes, peas, apples, oranges, lemons, mandarins, bananas. In addition, with this form of the disease, Betaine is prescribed for children up to 3 years of age starting with 100 mg / kg / day, children over 3 years old and adults 3 grams 2 r / day.

Deficiency of protein is replenished with the use of special mixtures of amino acids (without methionine) - Anamiks, Homidon, Analog, Max.

Along with such a diet, patients need an additional source of calcium and iron, which is supplemented with medicines (Calcium gluconate, Sorbifer, Fenuils, Tardiferon and others).

The effectiveness of diet therapy is checked by the content of methionine and homocystin in blood and urine.

Since the disease is accompanied by an increase in blood coagulability, such patients are shown a constant intake of antiaggregants in small doses (for example, Aspirin or Cardiomagnola).

In the complex therapy can be used drugs that improve blood circulation, nootropics, hepatoprotectors. In this case, they have a symptomatic effect. Also, depending on the clinical symptoms, patients are shown physiotherapy, physiotherapy exercises, massage sessions, acupuncture.

Thus, homocystinuria is a rare hereditary disease that affects many organs in the human body. If the disease is diagnosed early, the patient can be helped to avoid the appearance of severe symptoms with the help of diet or vitamin B6, depending on the form of homocystinuria.