It is about a more frequent disease since its incidence is 1 per 15 000 births (50 to 60 cases a year in France).
The P.C.U. is related to the absence of an enzyme, the phenylalanine hydroxylase, which normally makes it possible to transform phenylalanine into tyrosin.
This blocking of the catabolism of phenylalanine involves an increase in its blood rate, (normally lower than 4 mg/ml). This accumulation will injure the cerebral cells and to involve an encephalopathy very serious A a certain rate of phenylalaninemy (15 - 20 mg/ml), there is passage in the urines of acid-ph�nyl-pyruvic and by an additional metabolic way (hydroxylation in ortho whereas tyrosin is hydroxylated as a para) hydroxy-ph�nyl-pyruvic formation of acid ortho-.
The disease was discovered by chance by F�lling, a biochemist. Examining two children enc�phalopathes same fratrie, it obtained, by adding iron perchloride to their urines, an unexpected green colouring. It discovered that it was due to the ph�nyl-pyruvic presence of acid and showed the mechanism of the disease which it called " ph�nyl-pyruvic idiocy ".
In the years 1950, Bickel showed that by bringing the children to normal operating condition deprived or very low in phenylalanine, one avoided encephalopathy.
The private clinic is very poor and is practically reduced to the appearance of an encephalopathy during first months of the life. There are neither malformations, nor dysmorphie, it is a " naked encephalopathy ", but, on the other hand, the convulsions are frequent and in particular the serious epilepsy of spasms type in inflection.
This encephalopathy can be avoided by the mode which must be instituted as pr�coc�ment as possible, as of the first days of life. It is to say the interest of the tracking n�onatal applied systematically to all the French new-born babies.
The search of the ph�nyl-pyruvic acid in the urines is an easy but too late test. Easy for the reaction to iron perchloride is done by soaking a strip in the urine : the strip transfers with the green in the presence of pyruvic acid ph�nyl-. But this reaction is abandoned as average of tracking for the appearance of acid ph�nyl-pyruvic is relatively late and requires a high rate and already poison of phenylalaninemy.
Tracking is thus done by measuring the phenylalanine rate (Pa) in blood. Blood is taken on a special blotting paper after puncture with the counterfoil. Blood must impregnate completely, recto-back, two of the circles of carton. This carton is then addressed, by the post office, at a regional approved laboratory where the proportioning of Pa is carried out.
This one can be done either by the test of Guthrie, or by fluorometry.
The diagnostic means used was the test of Guthrie a long time, biological test whose principle is as follows: to a medium of culture of bacilli subtilis, one adds an antagonist, the thi�nylalanine which prevents the push of the bacillus ; this antagonistic negotiable instrument can be raised by phenylalanine. A impr�g�n� blotting paper disc of blood is thus placed on a medium of culture of bacilli subtilis containing the inhibitor. Normally, the bacillus does not push. On the other hand, if there is Pa in blood tested, the bacillus pushes and the size of the colony will be all the more important since the quantity of Pa will be large. The comparison with pilot discs containing of the known amounts of Pa makes it possible to quantify the rate of Pa. It is thus about a quantitative but coarse proportioning. It rises from what has just been known as that the test of Guthrie cannot be made in children receiving of the antibiotics which would inhibit the push of the bacillus. It goes without saying also that it should be waited until the child is fed by milk containing of Pa to practise the taking away. The taking away must be made in J3 after 72 hours of life.
With little close everywhere, this tracking of mass is carried out by the fluorometry, method more precise. After �luat of the blotting paper disc , proportioning is quantitative and can be practised even under antibiotics.
A result of 10 mg/ml translates the existence of a hyperphenylalaninemy but any result reaching or exceeding 4 mg/ml is regarded as suspect and obliges to practise a new examination without delay. However, the child left maternity and it is necessary to alert the parents, the attending practitionar and the services of P.M.I. as soon as possible to make a new taking away and a new proportioning, with the need after administration for vitamin C (coenzyme) which, when the increase is related to immaturity, facilitates the return to a normal answer. If the rate of Pa remains high, the child must be directed towards a specialized center where complementary examinations: chromatography of the amino acids, proportioning of tyrosin, will be made and if the P.C.U. is confirmed, the child will be put at the mode. Pa being an essential amino acid, should be determined the acceptable rate. The mode will be low in proteins and those will be brought either by protein hydrolysats in which one will have eliminated Pa, or by mixtures of amino acids without phenylalanine.
In France, one uses especially Lof�nalac or Albumaid at the start, then with L?age of the diversified mode, food hypoprotidic.
As soon as possible, the child will be returned to his family and will carry out a life as normal as possible,; to establish an acceptable mode poses many practical problems which must be taught with the mothers with which one will give a range of menus established either according to the ponderal system, or according to the volumetric system. C?is to say L?importance D?a good collaboration between the doctor and the dietetician. At the beginning, control will be weekly then it will be spaced as from the sixth month. This control will be continued during years including during the schooling; the question of widening, to even stop the mode between 8 and 10 years is discussed.
The processing is now well codified and one must manage absolutely to obtain normal children. With time, this success now poses the problem of the descent of the girls treated for the P.C.U. as of the birth and which justifies that the girls continue to take dietary foodstuffs so that L?acceptability is correct the day when they will have to be given to the mode for their pregnancy : in the absence of this mode, the children of mother PCU will present: microcephalus, cardiopathy and backwardness.
The practice of systematic tracking made it possible to better
know the various forms of hyperph�nylalanin�mies. According to Rey, one can
distinguish :
- phenylalanine
hydroxylase deficits with variable the usual following :
� a null activity, it is traditional form P.C.U.,
� an activity to 3 %, it is the atypical or " Mediterranean " form,
� an activity from 3 to 6 %, it is the moderate form.
- deficits of the system cofactoriel characterized by an activity normal phenylalanine hydroxylase and:
� is a complete deficit of synthesis of the biopt�rines (deficit as neurotransmetteurs) giving a hyperphenylalaninemy,
� is an incomplete deficit giving of the pseudotransient forms,
� is a deficit in dihydropt�ridine r�ductase, cofactor necessary to the hydroxylation of tyrosin phenylalanine.
In these variable, the hyperphenylalaninemy is less low than in the P.C.U. traditional and falls brutally at the time of the mode. The tolerance with Pa is larger. The hepatic biopsy shows a normal activity of phenylalanine hydroxylase and it is then necessary to specify the metabolic block (urinary study BH4).
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