Kriegler-Nayyar Syndrome: Description, Causes, Symptoms and Treatment

It is quite rare to hear about thisdisease, like Kriegler-Nayyar syndrome. But, unfortunately, this diagnosis can put one child in a million. It may seem that this is an extremely rare disease, but today, in the age of genetics, mutations are detected very often. Let's consider what kind of disease it is and what is the treatment in this case.

History of discovery

It must be said that this syndrome was discovered ratherrecently, in 1952 of the last century. Two pediatricians, Kriegler and Nayyar, while observing newborn children, described for the first time the unusual symptoms of jaundice. Further studies led to the detection of pathology in the liver. In children, the indirect bilirubin was significantly increased, which subsequently had a toxic effect on the body as a whole. According to laboratory data, bilirubin was raised to 765 μmol / l, while remaining within these limits throughout the life of the child.

After some time colleagues found similarsymptoms in older children, but with one peculiarity. Bilirubin was raised only 15 times normal and during life decreased to normal. There was no toxic effect on the body. As a result of such observations, the disease received its current name: the Kriegler-Nayar syndrome, a description of which was first made by two pediatricians.

Description of the disease

The Kriegler-Nayar syndrome is a geneticdisease. Clinic disease is expressed in vivid jaundice and severe neurological disorders. Jaundice is detected in the first hours after birth and persists throughout life. Lesions occur in equal measure both in boys and in girls. Since jaundice is a manifestation of problems with the liver, in some patients this organ is enlarged in size.

Signs of the defeat of the central nervous system arise in infancy,at times in the first days of life. They are expressed in muscle tension, involuntary twitching of the eyes, arching of the back, and convulsions. Sick children, as a rule, lag behind in mental and physical development. There are two types of this disorder. Syndrome Kriegler-Nayyar 1 and 2 types can have different symptoms.

Symptoms of type 1

Unfortunately, the Kriegler-Nayar type 1 syndromecharacterized by a progressive course. The first symptoms appear in the first hours of life. The baby becomes more pronounced yellowness of the whites of the eyes and skin, which is different from the usual postpartum jaundice. It does not go away in a few days, and the symptoms are accompanied by cramps, involuntary movements of the body and eyes. After a while, you can see a slowdown in mental development associated with bilirubin encephalopathy.

Indicators of free bilirubin in analyzesincrease to 324-528 μmol / l, in fact, it is above the norm by 15-50 times. Intoxication of the brain in this case leads to a lethal outcome in a short time. In exceptional cases, such children survive to school age.

Symptoms of type 2

The first signs of the disease appear significantlylater than at type 1. Disease can manifest itself in the first years of life. In some children, jaundice does not appear until adolescence, and neurologic abnormalities are rare. Symptoms are similar to type 1, but not so severe. Bilirubin encephalopathy can occur after an infection or severe stress.

Biochemical parameters of blood at type 2 are muchbelow - the level of bilirubin is about 200 μmol / l. This indicator indicates that the activity of the enzyme glucuronyl transferase is less than 20% of the norm. In bile there is bilirubin-gljuguronid. Diagnosis with "Phenobarbital" is positive.

Bilirubin encephalopathy

What is terrible about Kriegler-Nayyar syndrome? Symptoms of the disease are manifested in brain poisoning in four phases. In the first phase, the baby behaves apathetically and very sluggishly. This is manifested in poor sucking, relaxed state, a sharp reaction to extraneous sounds. The cry of the baby is monotonous at the same time, it often spews up and even vomiting may open, his look wandering, as if he has lost something. Breathing can be slow.

The second phase can last from a few days toseveral months. The child becomes tense, the muscles of the body take an unnatural position, the handles are constantly compressed into a fist, the back arches with an arch. The cry from the monotonous turns into a very sharp one, the sucking reflex disappears and the reaction to the sounds. There are convulsions, snoring, loss of consciousness.

The third phase is manifested by a period of false improvement in the state. All previous symptoms disappear for a while.

The fourth phase may appear on the 5th month of lifeand manifest themselves as obvious symptoms of physical and mental retardation. The kid does not hold his head, does not follow the moving objects, does not react to the voice of close people. He develops convulsions, paresis, paralysis. Unfortunately, brain poisoning at type 1 occurs very quickly, and the baby dies in infancy.

Causes of the disease

The main cause of the disease lies in the genes. In them, the process of formation of a certain enzyme, which is responsible for the production of bilirubin, is disrupted. For the most part, this disease affects the Asian population of the planet. The mutating gene is transmitted by an autosomal recessive type. In this case, both parents of the baby can be carriers of the mutation, but themselves be healthy. One of the parents can also be a carrier, then the probability of manifestation of the disease will be 50 to 50%.

Hereditary mutation of the gene leads to the fact thatthe body is not able to bind free bilirubin with glucuronic acid. And this, in turn, leads to the fact that free bilirubin poisons the body, penetrating the blood-brain barrier, which in new-born children does not function. The brain of the child is exposed to poisoning, where toxic bilirubin accumulates.

Treatment

For children who are diagnosed with a syndromeKriegler-Nayyar, the treatment is aimed at removing from the body free bilirubin. It is also important to prevent the development of toxic brain damage.

For its treatment, drugs are used,increasing the activity of uridine-diphosphate-glucuronidase, an enzyme leading to irreversible processes in the liver. For this, "Phenobarbital" is used in a dosage of up to 5 mg per kilogram of body weight per day. It should be noted that it positively affects exclusively Kriegler-Nayyar type 2 syndrome. At 1 type the organism on "Phenobarbital" practically does not react.

For both types of illness, sessions are heldphototherapy, plasma is introduced, exchange blood transfusions are performed. All procedures are prepared for performing liver transplantation - for children with type 1 this is the only chance to survive.

Diagnostics

To date, medicine is able to establishthe causes of diseases such as Kriegler-Nayyar syndrome. Symptoms and methods of treatment have been described for a long time, and now with the help of DNA tests it is possible to predetermine a genetic predisposition to diseases still in utero. After the birth of the baby, DNA diagnosis provides an accurate answer about whether there is a mutation in certain genes.

Also, with developing jaundice, a trial with "Phenobarbital" is done. The result of the analysis shows the type of disease.

If you suspect a Kriegler-Nayar syndrome, the parents will have an anamnesis and carry out DNA tests to confirm the diagnosis.

Prevention of disease

Preventive measures in the Kriegler-Nayar syndrome are to prevent the occurrence of complications.

With Type I syndrome, it is very important to prevent the development of bilirubin encephalopathy, because it leads to premature death of the patient.

With type II syndrome, prevention is reduced toinform the patient of the circumstances that may provoke an exacerbation of the disease. These are complicating infections, overstrain, pregnancy, acceptance of alcohol and medications without the supervision of the attending physician. All this can cause an increase in bilirubin in the blood and lead to severe intoxication. In this article it is impossible to describe all cases, because Kriegler-Nayyar syndrome (treatment, the causes, the symptoms of which are examined by us) can manifest itself in children individually.