Phénylcétonurie

The phénylcétonurie is a serious Genetic disease in relation to a disorder of the metabolism of the Phénylalanine (Amino-acid of food origin). It affects a newborn on 16 000 and is responsible for a mental backwardness progressive in absence of suitable Traitement.

History

The phénylcétonurie was discovered by the Norwegian doctor Ivar Asbjørn Følling, in 1934, when it observed that the hyperphenylalaninemy (HPA) was associated with a backwardness. In Norway, this disease is called disease of Følling , according to that which discovered it. Benzoic acid, which led him to conclude the compound contained has Benzene boxing ring. Further testing showed the Melting not to Be the same ace Phenylpyruvic acid which indicated that was the substance in the urine. His careful science inspired many to pursue similar meticulous and painstaking research with other disorders. -->Les patient reached this disease cannot eat certain food like the chocolate, milk etc…

Genetics

In the cells of the liver, a Enzyme, the PAH (Phenylalanine hydroxylase), allows to transform phenylalanine into excess in Tyrosine (other amino-acid). At the individuals phenylcetonuric, the Gène responsible for the PAH is defective. It is a hereditary feature autosome recessive. There exists a rarer alternative, in which the PAH is normal, but where its cofactor, the Tétrahydrobioptérine (BH₄) is not synthesized by the patient.

At the phénylcétonuriques ones, the transformation of phenylalanine cannot occur and phenylalanine accumulates then in the Sang whereas the tyrosin rate is lowered. The phenylalanine excess in blood is toxic for the Nervous system, and disturbs the development of the Cerveau of the child, involving a backwardness. The lowering of the tyrosin rates involves a lowering of the production of Mélanine, with the result that the children reached tend to have a pale hair, dye and eyes. The phenylalanine excess is converted into phénylcétones (in particular the Phenylpyruvic acid) which will be excreted in the urine, from where the name of the disease. The sweat and the urine of the child reached have a typical odor which had with the presence of ketones.

Genetic representation

The gene holding information on the manufacture of the PAH present in the mankind several Allèle S. It is localized on the Chromosome 12.

Normal allele: ACAATACCTCGGCCC

Individual reached: ACAATACCT' You GGCCC

The individual reaches presents a difference to the tenth Nucléotide.

Diagnosis

The problem is easily detectable in the days which follow the birth thanks to a small sample of blood: the Test of Guthrie of the name of Robert Guthrie, the doctor who developed this test. For that, tracking of the phénylcétonurie is practiced in routine in the majority of the industrialized countries (in general combined with the examination of the thyroid function and other metabolic diseases .

Formerly the diagnosis was done by the observation of certain symptoms and the presence in the urine of alternate products of the metabolism. Today, the research of the presence of a phénylcétonurie constitutes the typical example of a reasonable screening, i.e. of an examination of tracking to recognize in an early way a disease. The test of Guthrie is thus a simple examination, without complication, good market and rapid, which results in diagnosing in an unquestionable way and in time a grave disease but for which it exists a strategy of treatment suitable and quite clear. What is essential, it is that all the new-born babies are examined as of the first days of life. This screening for new-born babies is of use in Austria since 1966 and each year from 8 to 10 new cases are diagnosed and can receive the corresponding treatment. In Germany, the test of Guthrie since was replaced by the mass spectrometry out of tandem which makes it possible to widen the screening of the new-born babies to the other disorders of the metabolism of the amino-acids like to different other congenital and curable diseases.

After having noted the result by screening, one still proceeds to a definition by chromatography on column of the phenylalanine concentration for confirmation. Before beginning a mode, one needs initially a test of load of tétrahydrobioptérine, a control in the urine of the bioptérine and the néopterine as well as a definition of the activity of the enzyme dihydroptéridinereductase (DHPR) in the red globules (érythrocytes) to exclude an atypical phénylcétonurie, since this one claims another therapy.

A prenatal diagnosis which consists of an examination of the amniotic liquid (amniocentèse) makes it possible as of the pregnancy to note in mothers presenting a phénylcétonurie if the child to be born is itself carrying this defect of the metabolism. Since the disease is transmitted in a recessive way, a healthy father can be carrying this genetic mutation. In such a case there would be for the child, if the mother would be reached, a risk of 50% to contract the disease according to the phenotype, since the child will automatically receive the tare of his mother, and with a probability of 50% that of the father hétérozygote.

Data

Treatment

The children are systematically detected at the time of the Test of Guthrie to the birth. The child reached can live with a normal cerebral development, while following a mode low in phenylalanine . nut S, Cheese and other dairy products. Starchy foods such ace Potato be, Bread, Pasta, and corn must also Be avoided. In those patient with has deficit in BH₄ production, treatment consists off giving this cofactor ace has supplement. -->

It is about a mode in which one removes any meat, fish, egg, i.e. any food which can contain protein producing phenylalanine. However, it is necessary to add to this treatment of compressed of Amino-acid essential contained in this type of food, to avoid a lack of these acids.

Phénylcétonurie in the mother

When women suffer from phénylcétonurie, it is essential for the health of their child to maintain low phenylalanine levels before and during the pregnancy. Although the fetus under development can be only one vector of gene of phénylcétonurie, the intra-uterine environment can comprise levels of phenylalanine very high, able to cross the placenta. The result is that the child can have a congenital disease of the heart, a delay of growth, a microcephalus and a mental deficiency. The women reached of phénylcétonurie themselves are not threatened of additional complications during the pregnancy.

In the majority of the countries, one advises with the women reached of phénylcétonurie and who want to have children to lower their phenylalanine levels in blood before they become pregnant and to carefully control their phenylalanine levels during all the pregnancy. One does it by regular analyzes of blood and a mode to be followed strictly, in general under the daily control of a dietician specialist in the metabolism. When the phenylalanine levels are low maintained for the duration of the pregnancy the risk of congenital anomalies is not higher than in the case of a baby of a mother unfulfilled of phénylcétonurie. The babies reached of phénylcétonurie can drink mother's milk. Certain research showed that an exclusive food with the center for the babies reached of phénylcétonurie can compensate for the effects of deficiency, even if during breast feeding the mother must maintain a mode strict to preserve low phenylalanine levels. Other research is necessary.

Sources

www.pcu.ch

External bonds

Association “Will-o'-the-wisps”
Forum in French
Phénylcétonurie on the site of French Association for the Tracking and the Prevention of the Handicaps of Child (AFDPHE)
International forum
Waiter of information for the orphan diseases
pdf on the medicamentous phénylcétonurie and its treatments

Simple: Phenylketonuria

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