What Is Homocystinuria?

Chinese name: homocystinuria

Homocystinuria

Homocystinuria is a genetic disease caused by the lack of cystathionine synthase during the methionine alienation process. Accompanied by symptoms such as mental retardation, developmental disability, abnormal lens position, rigidity of limbs, thinning hair, abnormal cardiovascular system and other symptoms, the individual died due to the formation of thrombus. Homocysteine is an intermediate metabolite of methionine, which together with serine can form cystine through cystathionine under the catalysis of cystathionase.

About homocystinuria

Chinese name: homocystinuria

Homocystinuria English name: homocystinuria

Alias: homocystinuria; pseudo Marfan syndrome

Homocystinuria or homocystinuria, also known as pseudo Marfan syndrome, is one of the sulfur-containing amino acid metabolic diseases is an autosomal hereditary metabolic disease. The mutant gene may be located on the short chromosome 2 The arms were first reported by Carson and Neill and Gerritsen et al. (1962). The incidence rate is 2.5 / 100,000 to 5 / 100,000 live babies. In addition to skeletal abnormalities and eye diseases, this disease can cause vascular and brain diseases. Children's stroke should be ruled out.

Causes of homocystinuria

Homocystinuria is an autosomal hereditary metabolic disease, and the mutant gene may be located on the 2nd

Homocystinuria Short arms of chromosomes. It is caused by sulphur-containing amino acids (methionine, cystine) degradation and metabolic disorders.

Homocystinuria epidemiology

No authoritative and comprehensive statistical data on the incidence of amino acid metabolic diseases has been found. The incidence of homocystinuria is reported in the literature from 2.5 / 100,000 to 5 / 100,000 live infants.

Pathogenesis of homocystinuria

The disease is caused by catabolism of sulfur-containing amino acids including methionine (methionine) and cystine.

Homocystinuria At least 5 types of enzyme activity deficiency have been found:

1.Cysteine synthase deficiency (classic)

(1) The typical bone manifestation of the patient is a thin and fragile body with tall, slender limbs, weak spider-like digits, arched feet, scoliosis, and kyphosis, such as pale yellow, rare, and crisp skin. There are reticular plaques that can cause one or both eyeballs to shift, usually downward shifting mental retardation. ^[1]

(2) Mild mental decline is the only neurological abnormality, which is the difference between this disease and Marfan syndrome, and the latter's intelligence is not damaged. It can promote blood clotting and cerebral arterial thrombosis due to platelet abnormalities, which is obviously related to thrombotic and embolic arterial occlusion. Coronary cerebral arterial and renal arterial thickening and fibrosis may occur in the late stage of the disease, and some patients may die during puberty in adolescence. Coronary artery occlusion, myocardial disease can become a source of emboli in the cerebral artery, causing hemiplegia and aphasia.

(3) The increase of homocystine in blood, cerebrospinal fluid and urine is due to the deficiency of hereditary cystathionine synthase, which leads to an increase in plasma methionine levels.

2.5N-

Homocystinuria Methyltetrahydrofolate (MTHF) -homocysteine methyltransferase deficiency manifests as mental retardation, skeletal abnormalities in Marfan disease, ocular nystagmus, and occasional seizures when there is no lens shift in the side view , Thrombocytopenia and azotemia.

3.5,10N-methyl-tetrahydrofolate reductase (5,10N-methylidynel-netetrahydrofolatase) deficiency type In addition to bone abnormalities and ocular symptoms, weakened proximal muscle strength, myopathy-like gait, multiple cerebral infarction, dementia and seizures, and Polyneuropathy such as polyneuropathy may be related to folic acid deficiency. The symptoms of this type and the cyanocobalamin reductase deficiency type are relatively mild and the survival time is longer.

4. Cyanocobalamin reductase deficiency can affect the activity of a variety of enzymes, which are the main metabolic enzymes of vitamin B12.

5. Mixed enzyme deficiency is usually 5N-methyl MTHF-homocysteine methyltransferase and cyanocobalamin reductase deficiency.

Pathological changes: The most obvious lesions are systemic vascular lesions, such as thickening or fibrosis of the intima of coronary, cerebral, and renal arteries, and fragmentation of elastic fibers. At the same time, abnormal platelets are prone to form microthrombus and emboli in the cerebral arteries and cerebral veins, causing cerebral infarction. Coronary artery lesions in the lungs, kidneys and other blood vessels can cause myocardial infarction, homocysteine and other sulfur-containing amino acids to promote vascular intimal proliferation. The mechanism is unclear.

Diagnosis of homocystinuria

According to clinical symptoms, such as ocular symptoms such as typical skeletal developmental deformity, lens retardation, mental retardation, and mental decline, plasma homocysteine and methionine increase with thrombotic or embolic vascular occlusive disease.

Differential diagnosis of homocystinuria

This disease should be linked with other

Cystine Identification of Sulfur Amino Acid Metabolism. 1. Cystathioninuria was first reported by Harris et al. (1959). It is caused by cystathionin deficiency, which is manifested as mental retardation, abnormal behavior, skeletal deformity (acral hypertrophy), thrombocytopenia, and metabolic acidosis. In the urine

drug Some patients who excrete a large amount of cystathionine may not develop neurological symptoms and have normal intellectual development. Treatment of this disease with a large amount of vitamin B6 can achieve better results. 2. Hypermethioninemia (Hypermethioninemia) Perry et al. (1965) first described that metabolic defects may be due to lack of methionine adenosyltransferase activity often occurring in the same family. Infants are irritable and agitated within 2 months of birth, and gradually There are drowsiness and seizures. The smell of boiled cabbage is often on the body surface. Blood and urine methionine can also increase significantly. Other types of sulfur-containing amino acids can also appear. Children usually survive 2 to 3 months and die from bleeding complications.

3. Methionine malabsorption syndrome, also known as oasthousedisease, Smith and Strang (1958) first reported that metabolic defects are dysfunction of methionine transfer in the intestine, and can also affect other amino acid metabolism, which usually starts in infancy and is intelligent. Developmental retardation, slender hair of the whole body, lightening of paroxysmal fever, and seizures may have systemic orthostatic spasticity. The special odor chromatography of dried celery or boiled sugar in the urine revealed a large amount of -hydroxybutyric acid and a variety of amino acids in the feces. Treatment is primarily diet therapy that limits methionine intake.

4. Glutathioneuria, cysteine peptideuria -mercaptolactate-disulfide cysteineuria (-mercaptolactate-disulfide-cysteinuria) are rare metabolic defects of sulfur-containing amino acids, the main manifestations The main treatment for mental retardation and other neurological symptoms is to limit the corresponding dietary intake.

Homocystinuria test

Laboratory inspection

1. A large number of sulfur-containing amino acid sodium nitroprusside test can be strongly positive in urine, mainly homocysteine, homocysteine and methionine.

2. Plasma homocysteine and methionine levels increase, plasma antithrombin activity decreases, often with the tendency of intravascular thrombosis.

Other auxiliary inspections

1. X-ray examination showed bone deformities.

2. CT or MRI can show occlusive vascular disease, such as kidney and brain thrombosis and infarction.

Related inspections

Urocystine

Amino acid

Homocystinuria treatment

1. Strictly limit the intake of methionine in foods. Use a low-methionine diet.

Homocystinuria Restrict protein intake during childhood, sometimes intelligence can reach levels similar to normal children. Can take large doses of vitamin B6, 250 ~ 500mg / d, because it is a cystathionines synthetase coenzyme (cystathioninesynthetasecoenzyme) can reduce the secretion of homocysteine, and have a certain effect on the relief of neurological symptoms such as mental improvement. If vascular disease occurs, anticoagulants can prevent further occlusion of blood vessels.

2.5-N-methyltetrahydrofolate (MTHF) -homocysteine methyltransferase deficiency or cyanocobalamin reductase deficiency can be treated with vitamin B12, and methylene tetrahydrofolate reductase deficiency can be tested with folic acid Although the excretion of homocysteine in the urine was reduced after administration, the clinical symptoms did not improve. Treatment of symptomatic cerebral infarction.

Homocystinuria prevention

Treatment of genetic diseases is not satisfactory, and prevention is even more important. Preventive measures include avoiding genetic counseling, genetic testing of carriers, prenatal diagnosis, and selective abortion to prevent the birth of children.