Phenylketonuria

Phenylketonuria is a serious hereditary disease characterized mainly by the damage to the nervous system.

Etiology and pathogenesis. As a result of the mutation of the gene controlling the synthesis of phenylalanine hydroxylase, a metabolic block develops at the stage of conversion of phenylalanine into tyrosine, as a result of which deamination and synthesis of toxic derivatives - phenylpyruvic, phenyl-lactic and phenylacetic acids become the main way of phenylalanine conversion. In the blood and tissues, the content of phenylalanine is significantly increased (up to 0.2 g / l and more at a rate of 0.01-0.02 g / l). An important role in the pathogenesis of the disease is played by inadequate synthesis of tyrosine, which is a precursor of catecholamines and melanin. The disease is inherited by autosomal recessive type.

Clinical picture. Signs of phenylketonuria are found in the first weeks and months of life. Children lag behind in physical and neuropsychic development; Marked lethargy, excessive drowsiness or increased irritability, tearfulness. As the disease progresses, epileptiform seizures can occur-unfolded convulsive and non-convulsive types of nods, bows, jerks, short-term malfunctions. Hypertension of certain muscle groups is manifested in a peculiar "tailor's pose" (podzhatye legs and bent hands). There may be hyperkinesis, tremor of hands, ataxia, sometimes paresis on the central type. Children are often blond with light skin and blue eyes, they often have dermatitis, eczema, excessive sweating with a specific (mouse) smell of sweat and urine. A tendency to arterial hypotension is revealed. In the absence of treatment, idiocy or imbecility develops, a deep mental disability develops.

Diagnosis. It is extremely important to establish a diagnosis in the preclinical stage, or at least no later than the 2nd month of life, when the first signs of the disease may appear. For this, all newborns are examined according to special screening programs, which reveal an increase in the concentration of phenylalanine in the blood already in the first weeks of life. Each child who shows signs of delayed development or minimal neurologic symptoms should be examined for the pathology of phenylalanine metabolism. Microbiological and fluorometric methods are used to determine the concentration of phenylalanine in the blood, as well as Feeling's test for phenylpyruvic acid in the urine (adding a few drops of a 5% solution of ferric chloride and acetic acid to the patient's urine leads to the appearance of a green spot on the diaper). These and other similar methods belong to the category of orienting, therefore, with positive results, a special examination is required using quantitative quantitative methods for determining the phenylalanine content in blood and urine (chromatography of amino acids, use of amino analyzers, etc.), which is performed by centralized biochemical laboratories.

Children require special supervision and treatment in medical and genetic centers (offices of polyclinics).

Differential diagnosis is carried out with intracranial birth trauma, intrauterine infections.)

Treatment. When the diagnosis is confirmed by biochemical methods, children should be transferred to a special diet, with a restriction of phenylalanine, which, with early diagnosis, guarantees normal neuropsychological development of the child. Milk and other products of animal origin from the diet exclude and designate protein hydrolysates (cymogran, lefanolac, berlofen, hypofenate), which become the main food products that provide the need for protein. Protein hydrolysates are introduced with fruit and vegetable juices, mashed potatoes, soups. Treatment is carried out under the control of the content of phenylalanine in the blood, to maintain its level in the range of 0.03-0.04 g / l. Strict restriction of proteins of animal origin is required during the first 2-3 years of life.

Prevention. Of great importance is the special monitoring of the families of risk, that is, for such families where children with phenylketonuria already existed. Newborns from these families should be subjected to compulsory biochemical examination and with indications-early treatment. Detection and treatment of children through mass screening programs also helps to prevent the development of severe mental disability.

A DNA probe was proposed for prenatal diagnosis of phenylketonuria in high-risk families.