About the disease
Phenylketonuria (PKU) is a genetic disease associated with a metabolic disorder of amino acids, mainly phenylalanine. The intake of ordinary protein food into the baby's body leads to the accumulation of toxic metabolic products in the tissues. These compounds irreversibly affect the nervous system and brain of the child, causing progressive dementia.
In some countries, the disease is named after the discoverer and is called Völling's disease. Another name, phenylpyruvic oligophrenia, indicates the pathogenesis of the disease.
The statistics on the spread of hereditary disease differ from country to country. So, in Russia, the disease is found in one baby out of 5-10 thousand newborns (depending on the region of the country). The safest country in terms of the risk of developing phenylketonuria is Finland (1: 100,000). Turkey ranks first in the occurrence of a genetic disease, one in 2600 newborns has an impaired phenylalanine metabolism.
Among patients with phenylketonuria, girls are 2 times more likely than boys. Inheritance occurs in an autosomal recessive manner, which means the presence of a mutant gene in both parents' families. Healthy carriers of a genetic defect may not be aware of their own characteristics and may not have any external manifestations. The situation becomes more complicated when the owners of the mutation get married and are about to have children. The risk of having a baby with phenylketonuria in this case is 25%. Half of the children born to this family will remain asymptomatic carriers of the hereditary defect.
Although the disease can lead to gross, irreversible disorders in the development of the baby and significantly worsen the quality of life of the baby, unpleasant consequences can be avoided. Phenylketonuria is one of the few hereditary diseases that can be effectively treated. With timely measures taken, the baby almost always grows up healthy.
Historical reference
For the first time, the hereditary nature of dementia was suspected by the Norwegian biochemist and psychiatrist Ivar Asbjörn Fölling. Observing a group of mentally retarded children, the doctor noticed a common clinical picture and found a change in the chemical composition of the urine of sick brothers and sisters. By adding a solution of ferric chloride to the biological fluid, the doctor revealed a change in the color of urine, the appearance of an olive-green tint. The presence of changes in analyzes in close relatives gave rise to suspicion of hereditary causes of the disease.
This method of detecting phenylketonuria has not lost its relevance in the modern world. The determination of phenylpyruvic acid in urine is called Völling's test in honor of the Norwegian doctor.
How does the disease develop?
It is impossible to predict the development of phenylketonuria in a newborn baby without additional research. The baby is no different from his peers, looks like an absolutely healthy child. Changes occur within the body when enteral feeding begins, the proteins of breast milk enter the body.
The cause of the pathology lies in the lack of certain enzymes involved in the conversion of the essential amino acid phenylalanine to tyrosine. Thus, the level of phenylalanine and its derivatives in the blood and cerebrospinal fluid increases. Metabolic products have a toxic effect on brain cells, disrupt fat metabolism and the transmission of nerve impulses between neurons.
At the same time, tyrosine, necessary for normal functioning, is not synthesized in the proper amount. This amino acid is essential and takes an active part in the formation of hormones, neurotransmitters, melanin pigment.
There are several clinical forms of phenylketonuria, which are characterized by a deficiency of a certain enzyme in the liver. In 98%, PKU type I occurs, associated with a gene defect in the 12th chromosome. The disease is manifested by a lack of phenylalanine-4-hydroxylase and responds well to treatment. II and III types of the disease are extremely rare ailments and are characterized by severe manifestations, ineffectiveness of diet therapy in correcting amino acid metabolism.
Symptoms of the classic form of phenylketonuria
Common manifestations
If neonatal screening was not carried out in the maternity hospital, the disease remained unrecognized and the necessary treatment measures were not organized, then PKU will manifest itself in the first year of the baby's life. Parents will find the first signs of deviations from the norm in a child at the age of 2-6 months, when a previously healthy toddler becomes lethargic and apathetic, or vice versa, excessively irritable. Eating often ends with regurgitation, and manifestations of allergic dermatitis appear on the baby's skin.
Characteristic appearance
Since the violation of amino acid metabolism leads to a decrease in the formation of melanin, in the event of the development of the disease, the skin, hair, and the iris of the eyes lose pigment. Babies with a genetic disorder have blonde hair, thin pale skin, and blue eyes. A characteristic smell of sweat and urine of crumbs can indicate a hereditary ailment. Many doctors describe it as "mouse", and it is associated with the release of metabolic products of amino acids with biological fluids.
Damage to the nervous system
The first signs of changes in the nervous system are manifested by lethargy, a decrease in the muscle tone of the crumbs. Dystonia often occurs, involuntary muscle contractions, obsessive movements, and convulsions appear. Development of organic pathologies of the brain is possible - microcephaly and hydrocephalus.
Almost 50% of patients with phenylketonuria develop epilepsy. Sometimes the characteristic seizures are the first sign of a hereditary disease. Paroxysms are difficult to treat with conventional anticonvulsants and significantly reduce the child's quality of life.
Development lag
With the course of the disease, the baby quickly loses interest in the world around him, becomes apathetic. The physical development of the child also suffers - the baby late masters the necessary skills. A delay in mental development becomes apparent when problems arise in the formation of speech, a lag in mental development.
Studies have shown that gross changes in intellectual activity develop after a year of disease progression. The crumb irreversibly loses up to 50 IQ points annually, which subsequently leads to the development of debility, imbecily or idiocy. Therefore, the timing of starting treatment for phenylketonuria is very important.
Neurological problems in older children are expressed in hyperactivity, the appearance of stereotypes, obsessive movements of the hands, face, tongue, swaying. Sometimes mental disorders manifest themselves in schizophrenic states.
Severe developmental delay leads to a lack of walking skills in 30% of sick children and alalia, speech underdevelopment, in 60% of patients.
Varieties of pathology
Transient form of hyperphenylalaninemia
The disease does not always proceed classically, sometimes the increase in the level of phenylalanine is temporary, and the disease itself does not develop. A short-term increase in the concentration of amino acids in the blood of a child may be associated with the immaturity of the baby's enzyme systems, which is most typical for deeply premature babies. Such babies require a more detailed examination to determine the cause of the disease.
Pterin-dependent variants of phenylketonuria
Approximately 2% of babies who have been diagnosed with phenylketonuria in a maternity hospital and are prescribed an appropriate diet develop neurological problems. These symptoms may indicate the development of a rare, pterin-dependent form of PKU (type II, III according to the classification) in the baby. The clinical manifestations of atypical forms of PKU are similar to the course of the classical form, but the symptoms progress faster, and diet therapy does not have the desired effect.
A huge role in the development of pterin-dependent forms is played by a deficiency of neurotransmitters, which occurs due to a violation of amino acid metabolism. These substances are necessary for the transmission of nerve impulses between nerve cells, without which the normal functioning of the body is impossible.
Phenylketonuria II is considered more malignant than type III. Gross metabolic disorders of amino acids lead to massive death of nerve cells. Often, babies with progressive PKU type II die at the age of 2 - 3 years.
Maternal phenylketonuria
Children with PKU are not always born to healthy parents. If pregnant women with hereditary disorders do not follow a diet, there is a high probability of having a baby with maternal phenylketonuria syndrome. Toxic substances penetrate the placenta from the mother's body to the fetus and disrupt the formation of the child's organs and systems. Children are born with multiple congenital malformations, microcephaly, mental and physical retardation.
Diagnostics
Family medical genetic counseling
Expectant parents need to be especially careful if in the families of any of them there have been cases of the birth of children with phenylketonuria. It is impossible to exclude the possibility of the birth of a child with PKU, even if the disease manifested itself in a distant relative. The insidiousness of the disease lies in the asymptomatic carriage of the damaged gene by absolutely healthy people.
All couples who have suspicions of hereditary diseases in the family should consult a geneticist even during the planning of the baby. At the Medical Genetic Center (MGC), using modern diagnostic methods, it is possible to identify the carriage of a mutant gene and calculate the risk of having a child with PKU and other genetic diseases.
Invasive diagnostic methods (chorionic biopsy, amniocentesis, cordocentesis) can help determine the disease before the baby is born. In this case, the genetic material obtained from the fetus is examined. These methods are traumatic and can lead to spontaneous abortion. Therefore, their use is justified only with proven carriage of mutant genes in parents and a high risk of PKU in the baby.
Neonatal screening
Before being discharged from the maternity hospital, newborn babies are massively examined for hereditary diseases. For this important study, the health worker draws blood from the baby's heel and applies droplets of biological fluid to the filter part of the test blank. Each drop of blood is designed to detect one of 5 diseases: phenylketonuria, cystic fibrosis, congenital hypothyroidism, adrenogenital syndrome, galactosemia.
Neonatal screening is a very important and necessary examination for all children without exception. It is carried out completely free of charge and is aimed at preserving the health of the nation. By refusing to manipulate, parents make a huge mistake, because the symptoms of hereditary ailments are not always noticeable in a newborn baby. Vivid clinical manifestations often arise when it is already difficult to help the child, and the changes in the body of the crumbs have become irreversible.
This method is reliable in detecting phenylketonuria, if the baby receives a sufficient amount of enteral nutrition, breast milk. Therefore, newborns who are in the intensive care unit are analyzed later. The timing of the test in full-term and premature babies also differs. For babies who appeared on time, a set of capillary blood is recommended on the 4th day of life. The study for prematurely born crumbs is postponed until 7 days.
The analysis should be performed on an empty stomach, which will provide a more accurate result and increase the diagnostic value of the test. The form with the baby's blood droplets and the parents' passport data is sent to the laboratory of medical genetic consultation, where a biochemical study is carried out.
Parents need to pay attention to the correctness of filling out the form, the correctness of their contact information. The study takes an average of 10 days, and the family is usually at home by this time. If a positive test result is found, parents will need to contact the medical genetic center as soon as possible, and incorrect contact information will delay further examination of the baby.
Examination of a child at the Moscow City Center
To confirm the disease in the baby and establish its cause, the baby will have to go through a multi-stage examination procedure. Repeated biochemical tests will help confirm an increase in the level of amino acids in the blood and make a decision about the need for diet therapy. A study of the levels of phenylalanine and tyrosine, the activity of liver enzymes, the determination of the metabolic products of amino acids in the urine are being carried out.
Then, molecular genetic diagnostics is carried out, which makes it possible to identify a mutation in the RAS gene responsible for the development of phenylketonuria. Using these methods, it is possible to determine the asymptomatic carriage of the disease.
PKU treatment
The most effective method of treating the classical form of phenylketonuria is considered to be properly organized diet therapy. Only by excluding foods containing a large amount of amino acids from the diet of crumbs can we expect positive results from the treatment.
Features of diet therapy
Rules for the selection of food products
Phenylketonuria in children is a difficult disease and only a doctor can choose the right diet for a baby. When choosing permitted products and calculating their volume, the doctor takes into account some individual characteristics:
- what form of the disease is present in the baby;
- the severity of the disease, the level of phenylalanine in the blood;
- the age of the crumbs;
- features of the physical development of fidgets;
- the physiological need of a growing organism for protein;
- how the baby tolerates the intake of a small amount of phenylalanine from food.
The amino acid phenylalanine is irreplaceable, which means it can only be ingested with protein foods. A growing child needs a sufficient supply of nutrients, because about 40% of dietary phenyalanin is spent on building their own proteins. It turns out that it is also impossible to completely exclude dangerous products from the diet of crumbs. Therefore, in the first days of diet therapy, it is assessed in the laboratory how the crumbs' body reacts to a small intake of amino acids with food.
Is breastfeeding possible with phenylketonuria?
Since, in most cases, the disease is determined in the first weeks of the baby's life, the question arises about the safety of feeding the baby with breast milk. In fact, breastfeeding is necessary for the normal development of the child, the formation of his immune system. But its use is justified only in cases where the mother adheres to clear rules and strictly controls the amount of food eaten by the baby.
For safe feeding, it is better to use freshly expressed breast milk, the allowable amount of which is calculated by the doctor based on the baby's body weight and his need for phenylalanine.
The younger the child, the higher his need for amino acid. For example, the allowable amount of phenylalanine for a newborn baby is 90 - 60 mg / kg of body weight per day, while the required amount of amino acid for a schoolchild is reduced to 10 - 20 mg / kg of body weight. The amount of phenylalanine in foods can be calculated given that 1 g of protein contains about 50 mg of the amino acid.
Specialized mixtures
There are specially designed products for the rational nutrition of children with phenylketonuria. They are made on the basis of protein hydrolysates or a mixture of amino acids, which are completely or partially devoid of phenylalanine. Nutrition with medicinal mixtures is aimed at replenishing the body with the necessary protein, sufficient supply of nutrients. These formulas can be used as breast milk substitutes or used as an addition to the main diet for older children.
The composition of medicinal mixtures for children of different ages is different. For example, products such as "Afenilak", "Lofenalak" are suitable for children under one year old. Older children are shown "Tetrafen", "Phenyl-free", "Maxamum - XP".
"Food traffic light"
Every year the baby grows, and his needs for food are increasing. It's time to introduce complementary foods, to try new dishes. Parents need to remember about the dangers of phenylalanine to the baby's brain, choose only foods approved by the doctor.
The diet of a sick child is significantly different from that of peers. Complementary feeding begins with the introduction of vegetables and fruits, then protein-free pasta, some types of cereals should be added. The attending physician should compose the baby's first menu and control the amino acid content in the blood against the background of changes in the diet.
All products are divided into groups according to the content of phenylalanine in them:
- red list.
It is recommended that you completely eliminate foods on this list as they are rich in protein. These are meat and offal, fish, eggs, bread, buckwheat, barley groats, Hercules flakes;
- yellow list.
It is permissible to use a small amount of products from this group under the control of a blood test. Perhaps the introduction of corn and rice groats, potatoes, dairy products with a low protein content;
- green list.
These products form the basis of nutrition for older children with phenylketonuria: corn and rice flour, most vegetables, fruits and berries, sweets, butter.
When using finished products, you must carefully read the instructions on the packaging. Eating bananas, dried fruits, and legumes can increase the concentration of phenylalanine, so their intake should be limited.
Other therapies
The use of medications is justified only for the treatment of pterin-dependent forms of PKU, when the diet does not have the desired effect. In such situations, drugs L-dopa and 5-hydroxytryptophan are used.
In other cases, it is possible to use vitamin therapy, mineral complexes, as an addition to the diet. If necessary, nootropic drugs, anticonvulsants are prescribed. Working with speech therapists, psychologists, massage, physiotherapy also have a positive result in the treatment of the disease.
Forecast and prevention
The course of the classical form of the disease does not significantly affect the life expectancy of a person. But without proper treatment, severe symptoms of the disease significantly affect the patient's intelligence and quality of life. In the case of rational diet therapy and timely control of the level of phenylalanine in the blood, children with PKU do not differ from their peers and adapt well in society. Atypical forms of the disease often lead to disability and death of the child, since treatment rarely has a good result.
Experts recommend following a diet throughout a person's life, but some relief is possible when a child reaches 18 years of age. Particular attention should be paid to pregnant women with PKU in order to avoid the syndrome of maternal phenylketonuria in a child.
Prevention consists in the prevention of closely related marriages, medical and genetic counseling of families at risk for the development of PKU, and a mass screening of newborns.
Conclusions
A baby's illness is a huge stress and test for young parents, especially if the illness is hereditary. But phenylketonuria is one of the few genetic diseases for which treatment interventions bring good results.
Parents need to understand the importance of neonatal screening and early, well-chosen diet therapy. It is worth carefully following all the recommendations of the attending physician and then such a terrible diagnosis as phenylketonuria will not become a sentence for the child.
