HOMOCYSTINURIA (grech, hom[oi]os similar, the same + cystine + grech, uron wetting) — the hereditary disease caused by disturbance of exchange of methionine, which is characterized by defeat of connecting fabric, nervous, bone, muscular and cardiovascular systems. It is inherited on autosomal recessively type (see. Inheritance ). It is for the first time described in 1962 by Carson and Neill (N. A. J. Carson, D. W. Neill). By 1968 it is described apprx. 80 observations of this disease [P. Mozziconacci et al.]. In 1970 Schmidt and Lyutts (Schmidt, Lutz) for the purpose of clarification of frequency of G. conducted survey of 103 medical institutions of Central Europe and received the notice on 29 cases; possible frequency of G. in Europe makes about 1: 3 000000. Possibly the disease meets considerably more often, but G.'s diagnosis is made seldom due to the lack of methods of identification of a gomotsistein, available to broad practice. According to Knapp (And. Knapp), G. takes on frequency the second place after a fenilketonuriya.
The etiology, a pathogeny and pathological anatomy
is the cornerstone of a disease the metabolic block on the way of transformation of a gomotsistein in tsistationin, connected with hereditary insufficiency of enzyme L - serines-dehydratases (tsistationinsintetaza; KF 4. 2. 1. 13). Thereof in fabrics excess of methionine and homocystine collects, concentration of a tsistationin and cystine in blood and urine decreases. According to Jackson (S. The N of Jackson), homocystine sharply breaks structure of collagen and elastin, forming with the lizilny remains of connection of tiazinovy type. Besides, the increased maintenance of metabolites of methionine in blood and fabrics exerts toxic impact on a nervous system. At gistol, a research of a brain of the dead from G. the centers of a focal necrosis and a gliosis are revealed.
The clinical picture
the Clinical picture of a disease is characterized by a delay of psychomotor development; children late begin to sit, go, speak. Sick G. are easily excitable, irritable. Intellectual development is, as a rule, reduced though patients with normal intelligence are observed. Spasms, hyperkinesias are possible. On EEG signs patol, activities are noted. Changes of a skeleton at many sick G. are similar to changes at Marfan's syndrome (high growth, a spider finger, a kyphoscoliosis, deformations of a thorax). Similarity is supplemented with the sign, general for these two diseases — damage of eyes (see. Marfana syndrome ). At G. the ectopia and an incomplete dislocation of a crystalline lens, a cataract, glaucoma, a degeneration of a retina are observed. At certain patients the atrophy of optic nerves, decrease in convergence, squint, a nystagmus comes to light. Moderately expressed symptoms of increase in intracranial pressure meet.
Frequent manifestation of G. are the vascular embolism of easy, renal arteries, fibrinferments of arteries or veins. As well as at Marfan's syndrome, the stratifying aortic aneurysm, defeat of an internal cover of vessels can be observed. On skin angiomas are possible. In some cases reveal inguinal hernias, a divarication of recti. Changes of the motive sphere are considerable: hypomyotonia, looseness of joints. Gait of patients is characteristic, to-ruyu one authors compare with duck, others call Chaplin's gait. Pyramidal frustration are occasionally noted: the spastic phenomena, increase in tendon jerks with expansion of a reflexogenic zone. Various vegetative and trophic symptoms are frequent: a hyperhidrosis, a xeroderma, a Crocq's disease, etc. Nevrol, the symptomatology is caused by disbolism in a brain, first of all exchange of serusoderzhashchy amino acids. Heavy focal cerebral frustration (a hemiplegia, etc.) can be caused by thrombosis of brain arteries.
Hair at sick G. thin and rare. After coloring of a bunch of hair acridic orange in an ultraviolet light orange-red fluorescence whereas at healthy people — green comes to light. And though the amino-acid structure of hair is not changed, the specified sign demonstrates change — SH bonds in tissues of a hair.
Content of methionine in blood of patients can reach 29 mg of % (norm of 0,4 — 0,45 mg of %); with urine more than 200 mg of homocystine are removed per day. Besides, in urine find fractions of the mixed disulfides of gomotsisteina-cystine.
At a loading test it is established that at sick G. sulfur of I-methionine passes not into I-cysteine, and into the inorganic sulfates removed with urine.
the Diagnosis is made on the basis a wedge, pictures and datas of laboratory. Screening test is offered (cyanide - nitroprussiate reaction with urine). At positive takes analytical methods of definition of methionine, homocystine, a tsistationin and cystine (paper chromatography, a high-voltage electrophoresis, the aminoacid analyzer) are applied.
Treatment consists in restriction of protein: patients receive 1 g of protein on 1 kg of weight; protein hydrolyzates, almost free of methionine are offered. Add cystine to 500 mg a day to food. High performance of pyrotoxin is noted.
the Forecast at observance of a diet favorable.
Bibliography Veltishchev Yu. E., etc. Homocystinuria, Pediatrics, No. 3, page 49, 1972; Gusev E. I. Clinical and biochemical studying of some hereditary diseases of a metabolism with defeat of a nervous system, Zhurn, a neuropath, and psikhiat., t. 71, No. 10, page 1475, 1971; Makkyyusik V. A. Ancestral features of the person, the lane with English, page 379, M., 1976; Mc To u s i with k U. Heritable disorders of connective tissue, St Louis, 1972; The metabolic basis of inherited disease, ed. by G. B. Stanbury a. o., N. Y., 1972; Mozziconacci P. e. a. Les maladies m6taboliques des acides of amin£s avec arri6ration men tale, P., 1968.
BB. E. Veltishchev; E. I. Gusev (not BP.).