Phenylketonuria in children is a violation of the hereditary amino acid metabolism due to a lack of liver enzymes that are involved in metabolism. At the same time, phenylalanine is converted into tyrosine. The early symptoms of phenylketonuria in a three-year-old child are vomiting, increased weakness (sometimes hyperactivity), delayed psychomotor development, mold smell from skin and urine. The most typical late signs of the pathological process include a lag in physical development, oligophrenia, the occurrence of seizures, eczematous changes in the skin, etc.
Screening for phenylketonuria in children is carried out in the maternity hospital. Further diagnosis involves molecular genetic testing. The main manipulations are determination of the level of phenylalanine in the blood, EEG, biochemical analysis of urine, and MRI of the brain. Therapy of this disease is to follow a certain diet. What kind of disease is phenylketonuria, we will consider in more detail below.
Features
Phenylketonuria (phenylpyruvic oligophrenia or Felling's disease) is a congenital, genetically caused disease characterized by impaired hydroxylation in the body of a substance such as phenylalanine, the accumulation of amino acids, as well as its metabolites in tissues and physiological fluids, with further damage to the central nervous system in severe forms.
Phenylketonuria in children (ICD code 10 - E70) was first described by A. Felling in 1934, with a frequency of 1 case per 10,000 children. In the neonatal period, this pathological process, as a rule, does not have specific clinical manifestations, however, the penetration of phenylalanine with food provokes the manifestation of the pathology already in the first half of life, and subsequently leads to serious violations in the development of the child. That is why the pre-symptomatic diagnosis of phenylketonuria in newborn babies is an important task of pediatrics, neonatology and genetics.
The main causes of development and variety
Phenylketonuria in children is a pathological process with an autosomal recessive nature of inheritance. This means that for certain clinical symptoms of the disease to occur, the child needs to inherit one pathological copy of the gene from both parents, who are heterozygous carriers of the defective gene.
Most often, a mutation of a gene that encodes the enzyme phenylalanine-4-hydroxylase and is located on the long arm of chromosome 12 leads to the development of such a disease. This is a classic type I phenylketonuria, accounting for 98% of all cases of pathology. Hyperphenylalaninemia in some cases reaches 30% or more. In the absence of therapy, this type of pathology is accompanied by severe mental retardation of the child.
In addition to the classical form, atypical phenylketonuria is distinguished, which proceeds with the same clinical symptoms, but can not be corrected with diet therapy. These include type II pathology (dehydroterin reductase deficiency), type III (tetrahydrobiopterin deficiency), and other, more rare forms.
The risk of having a baby with phenylketonuria increases significantly in closely related marriages.
Pathogenesis
The classic forms of phenylketonuria in children are based on a deficiency of the phenylalanine-4-hydroxylase enzyme, which is involved in the conversion of phenylalanine to tyrosine in liver mitochondria. In turn, tyramine, a tyrosine derivative, is the initial product for the production of catecholamines (norepinephrine and adrenaline), and diiodotyrosine for the formation of thyroxine. In addition, the formation of melanin is the result of the metabolic process of phenylalanine.
Genetically caused deficiency of this liver enzyme in children with phenylketonuria leads to a violation of the oxidative process in which phenylalanine comes from food. As a result, its level in the cerebrospinal fluid and in the blood (phenylalaninemia) increases significantly, and the concentration of tyrosine decreases accordingly. Excessive levels of phenylalanine can be eliminated by increasing the excretion of its metabolites with urine - phenyllactic, phenylpyruvic acid and phenylacetic acid.
Impaired amino acid metabolism is often accompanied by a change in myelination of nerve fibers, a decrease in the formation of neurotransmitters (dopamine, serotonin, etc.), which trigger pathogenetic mechanisms of mental retardation and progressive dementia.
Symptoms of phenylketonuria
How does this disease manifest? In newborns with phenylketonuria, as a rule, there are no clinical signs of a pathological process. Typically, the manifestation of this disease in children occurs at the age of 2-6 months. With the beginning of the introduction of complementary foods, proteins or its substitutes begin to enter the child's body, which leads to the appearance of the first, non-specific signs - weakness, sometimes - hyper excitability and anxiety, regurgitation, convulsive syndrome, muscle dystonia. One of the most common early pathognomonic symptoms of phenylketonuria is persistent vomiting, which is often mistakenly regarded as a sign of pyloric stenosis.
After the child reaches the age of 6 months, his lag in psychomotor development becomes noticeable. The kid becomes indifferent, less active, does not try to stand up or sit down, ceases to recognize loved ones.
The abnormal composition of sweat and urine causes a characteristic mold smell coming from the body. Often there is peeling of the skin, eczema, dermatitis, scleroderma.
In children with a similar pathology who are not receiving treatment, prognathia, microcephaly, enamel hypoplasia, and later teething may occur. There is a delay in speech development in a three-year-old child, and by about 4 years of age, there is a profound oligophrenia and a complete lack of speech and attention.
Body type
Children with phenylketonuria have a dysplastic physique, often vegetative dysfunctions (acrocyanosis, sweating, arterial hypotension), congenital malformations, they suffer from constipation and diarrhea. Their phenotypic features include light skin, hair and eyes. A child with phenylketonuria is characterized by a specific pose of a tailor (bent limbs), hand tremors, a mincing, shaky gait, and hyperkinesis.
2 and 3 type
The clinical manifestations of type II phenylketonuria are severe mental retardation, increased irritability, convulsions, spastic tetraparesis, tendon hyperreflexia. The progression of the pathological process can provoke the death of a child aged about 2 to 3 years.
With type III phenylketonuri, a triad of symptoms is observed: oligophrenia, microcephaly, spastic tetraparesis. The circumference of a child’s head is usually less than average by more than 2 standard deviations.
Diagnosis of the disease
At the present stage of development of medical science, the diagnosis of phenylketonuria (as well as congenital hypothyroidism, galactosemia, cystic fibrosis and adrenogenital syndrome) is included in special neonatal screening programs that are carried out for all newborns.
In which cases a puncture of the cerebrospinal fluid is done, many are interested. It is not included in the list of standard tests for the detection of phenylketonuria.
A screening test is done for 3-5 days of life (in case of full-term babies) and for 7 days of life (for premature babies) by taking a sample of capillary blood on a paper form. When establishing a phenylalanine level of more than 2.2 mg, the baby is sent to a child genetics for re-examination.
To confirm the diagnosis, the level of tyrosine and phenylalanine in the blood is checked, the activity of phenylalanine hydroxylase (liver enzymes) is determined, a biochemical study of urine (detection of ketonic acids) is carried out, and catecholamine metabolites in the urine. In addition, EEG and MRI of the brain are performed, a child is examined by a pediatric neurologist.
The circumference of the child’s head is measured.
A hereditary defect in phenylketonuria can be detected even at the stage of gestation during invasive prenatal diagnosis of the fetus (chorionbiopsy, amniocentesis, cordocentesis).
The differential diagnosis of this pathological phenomenon is carried out with intracranial injuries in newborns, amino acid metabolism disorders, intrauterine infections. In some cases, when conducting diagnostic measures, puncture of the cerebrospinal fluid may be performed.
Therapy and clinical guidelines
A fundamental factor in the treatment of this disease is the observance of dietary nutrition, limiting the intake of protein in the child's body. Therapeutic measures are recommended to be started at a phenylalanine level> 6 mg. For newborns, special mixtures are used - Lofenilak, Atenilak, for children over 1 year old - Phenyl-free, Tetrafen, after 8 years of age - Maxamum-HR, etc. low-protein foods - vegetables, fruits, juices, amino acid mixtures and protein hydrolysates should be a diet. Expansion of the diet is allowed after 18 years due to increased tolerance to phenylalanine. According to the provisions of Russian law, the provision of special nutrition for people suffering from phenylketonuria should be free of charge.
Patients are prescribed a variety of mineral substances, vitamins from group B, etc., as well as indications - anticonvulsants and nootropic medications. In the complex treatment of phenylketonuria, exercise therapy, general massage, acupuncture are widely used.
Toddlers who suffer from phenylketonuria should be monitored regularly by neuropsychiatric and pediatricians. In some cases, they need the help of a pathologist and speech therapist.
In addition, constant monitoring of the child’s neuropsychic status, monitoring of electroencephalogram indicators and the concentration of phenylalanine in the blood are necessary.
The atypical form of this pathological process, which cannot be treated by diet, requires the administration of anticonvulsant drugs, hepatoprotectors, replacement therapy with 5-hydroxytryptophan and levodopa. Clinical recommendations for phenylketonuria in children should be strictly observed.
Prevention and prognosis of phenylketonuria
Conducting a mass screening for the development of this disease in the neonatal period helps to organize early therapy and prevent serious cerebral injuries, impaired liver function. With the early use of the elimination diet in the development of classical phenylketonuria, the prognosis is pretty good. With late organized therapeutic measures, the prognosis of the child's mental development is very unfavorable.
Prevention of the negative consequences of phenylketonuria consists in the mass screening of newborns, early prescribing and long-term compliance with all the rules of special dietary nutrition.
In order to assess the likelihood of having a baby with phenylketonuria, genetic counseling should be given to couples who already have a sick child, as well as those who are in a consanguineous marriage, have relatives with a similar disease. Women with phenylketonuria and planning a pregnancy are advised to follow a strict diet before conception and during the gestation process to exclude an increase in the level of phenylalanine and its derivatives, and impaired development of a genetically healthy child. The probability of having a baby with phenylketonuria in such parents (carriers of the defective gene) is approximately 1: 4.
What is the diet for phenylketonuria in children?
Features of diet
Phenylalanine is an essential amino acid, and to ensure the growth and development of the child its exclusion is unacceptable, and in small quantities it must be ingested. Nutrition for the disease is based on three components:
- Special products - dry mixes for nutrition from a complex of amino acids without this amino acid.
- Specially selected food. The protein in them should be about 20% of the daily allowance.
- Low protein starch based foods.
The following products are excluded from children's nutrition:
- meat;
- bird;
- sausage;
- milk products;
- nuts
- eggs
- fish products;
- cereals;
- chocolate.
Berries, vegetables, fruits are allowed. But they should be introduced into the child’s nutrition only after counting the phenylalanine contained in them. You can eat ghee and butter, all forms of vegetable oils. Margarine and sour cream are allowed. From sweets honey, sugar, jam are allowed.
Children under 12 months are allowed to breastfeed, but to a limited extent. For babies on artificial nutrition, special mixtures with a low volume of protein should be used. The list of such mixtures includes:
- “Afenilak”;
- Lofenelac
- "MD mil PKU-0";
- "XP Analog LCP."
They have a composition as close as possible to breast milk. Such mixtures should be administered gradually over a period of 7 days.
The rules for starting complementary foods imply the introduction, first of all, of fruit juices from pears, apples, and plums. Giving them is allowed from 3 months, starting with a few drops, bringing the volume to 50 ml within a week. The second lure should be a protein-free cereal puree, jelly, cauliflower. You can cook them yourself or buy in a pharmacy. After 7 months, vermicelli, rice, spaghetti are allowed, and from 8 months - crackers, protein-free bread, crackers.
We examined what this disease is - phenylketonuria.