FENILKETONURYYa (synonym: a disease of Fellinga, a phenyl-pyruvic oligophrenia) — the hereditary disease caused by disturbance of exchange of phenylalanine, which is characterized by the progressing weak-mindedness.
For the first time F. it is described in 1934 by Felling (1. A. Foiling). Frequency F. among newborns, according to different researchers, averages 1:10 000. (See) occurs among patients with oligophrenias in 1 — 5% of cases.
Etiology and pathogeny. It is inherited on autosomal recessively type (see Inheritance). Lack of the enzyme of a fe-nilalanin-4-hydroxylase produced by a liver is the cornerstone of biochemical disturbances that leads to blocking of transformation of phenylalanine (see) in tyrosine (see). At the same time concentration of phenylalanine in blood increases to
15 — 20 MGTSOO ml and more (norm to
2,5 mg! 100 ml). As a result of deamination of phenylalanine it is formed alpha-toluic, phenyl-lactic, phenyl-pyruvic to - you, and also fenilatsetilglutamin, allocated much with urine. For the second time exchange of tyrosine and tryptophane is broken (see) that leads to insufficient formation of noradrenaline (see), adrenaline (see), dopamine (see Catecholamines), melanin (see). The described disturbances arise in the first days after the birth of the child, reach a maximum on 1 — the 2nd week and remain in the absence of treatment throughout all life of the patient.
Pathological anatomist and I. The main morphological changes are found in nervous tissue.
Reduction of the weight (weight) of a brain, a delay of myelination (see), formation of the centers of demyelination, the insignificant phenomena of a gliosis is noted a nek-swarm (see). Likvorny spaces of a brain are moderately expanded. In skin the quantity of melanocytes is reduced.
Clinical cards and - N and. For patients F. the light hair color and a blue iris of the eye of eyes is characteristic (children are always lighter than the parents and healthy brothers and sisters). In the first 2_3 months of life most of children looks absolutely healthy. Only at nek-ry of them slackness, drowsiness is noted, the concern is more rare. An early symptom is vomiting. A peculiar smell of urine of the child is noted (musty, mouse). By the end of the first half of the year of life 20 — 50% of sick children have eczematic changes of skin, sometimes considerable, at nek-ry the scleredema develops (see the Scleredema of newborns). At the same age the delay of mental development, edge begins to come to light, accruing, further leads to heavy weak-mindedness (see) — a deficiency of intellect or an idiocy. Only at insignificant number of patients defeat of the intellectual sphere is expressed unsharply. Lag in physical development is noted. Formation of movement skills is late. Many patients have spasms, to-rye can gradually disappear even without treatment, the gi-lerrefleksiya, the involuntary movements is found. At most of patients on EEG paroxysmal activity is registered. At nek-ry children the spasm of muscles of extremities is noted (preferential legs). All noted changes are characteristic of the patients who are not receiving since the birth of pathogenetic treatment.
The diagnosis is made in the first months of life on the basis of data a lab. researches. For identification F. at newborns use Guthrie's test (see Guthrie a method). At detection of the increased concentration of phenylalanine in blood (more than 4 mg: 100 ml) apply more exact quantitative methods of determination of content of this amino acid — an euzymatic method or a flyuori-metriya (see). Content of phenylalanine in blood at F. not less than 15 lg/YuO ml. In urine find feniliirovinogradny, alpha-toluic, phenyl-lactic to - you. At a research of urine use iron trichloride, at addition to-rogo urine Zine's hydra gets gryaznozeleny coloring, or 2,4 dinitrophenyl, at interaction about the Crimea urine grows turbid and becomes bright yellow. Apply also indicator
pieces of paper (fenistiks, the biofan) impregnated with iron trichloride to a research of a mo-'cha.
T. it is necessary to differentiate with a giperfenilalaninemiya, quite often observable at premature children in connection with insufficiency of enzyme of phenyl of lanin-4-hydroxy manholes. P ri
hyper phenyl of a laninemiya the content of phenylalanine in blood makes less than 15 mg! 100 ml. Giperfenilala-ninemiya usually disappears during 1 — 3 hmes., sometimes after appointment ascorbic to - you.
Treatment consists in sharp restriction of the protein arriving with food (depending on tolerance of an organism to it) and consequently, and phenylalanine. The number of the last shall not exceed 15 — 40 mg/kg (in the first months of life — 50 — 60 mg/kg). Exclude products with the high content of protein from food: meat, fish,
eggs, cheese, milk, peas, haricot, etc. Resolve sugar, fruit juice, natural and artificial honey, vegetable oils, an artificial sago. As substitutes of protein use various drugs, in to-rykh completely or almost completely there is no phenylalanine (lofenalak, tsimogran, Berlophenum, minafen). Milk, potatoes, bread, vegetables and fruit are appointed only after careful calculation of content of phenylalanine in them. It is necessary to keep to a diet not less than 6 — 7 years, and according to some researchers, and longer. The diet is necessary also for patients F. to women during pregnancy for avoidance of harmful effects of the ketonic acids collecting in an organism of the woman on a fruit.
P r about of N about z rather favorable. If treatment is begun on the first month of life and at the same time the level of phenylalanine in blood does not exceed 4 — 8 mg! 100 ml, are possible to achieve almost normal intellectual development of the child. What later begin treatment with, that it is less effective.
Prevention of mental retardation at children, patients F., consists in fuller coverage inspection of newborns for the purpose of early identification and correction of disturbances.
See also Hereditary diseases.
Bibliography: Lebedev B. V. and B of l of a fo-ma of N and M. G. Fenilketonuriya at children, M., 1972; F 0 1 1 i n g A. Uber Ausschei-dung von Phenylbrenztraubensaure in den Harn als Stoffwech selanomalie in Ver-bindung mit Imbezillitat, Hoppe-SevJ. Z. physiol. Chem., Bd 227, S. 169, 1934; Knapp A. Genetische Stoffwechselsto-rungen, S. 30, Jena, 1970; The metabolic basis of inherited disease, ed. by J. B. Stan-bury a. o., p. 240, N. Y. a. o., 1978;
Phenylketonuria, ed. by F. L. Lyman, Springfield, 1963; Phenylketonuria and some other inborn errors of amino acid metabolism, ed. by H. Bickel a. o., Stuttgart, 1971. B. V. Lebedev.