Crigler-Nayar syndrome: description, causes, symptoms and treatment

Довольно редко можно услышать о таком disease like Crigler-Nayar 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 look at what the disease is and what the treatment is in this case.

History of discovery

It must be said that they discovered this syndrome quiterecently, in 1952 of the last century. Two pediatricians, Crigler and Nayyar, observing newborn children, first described the unusual symptoms of jaundice. Further studies led to the identification of pathology in the liver. In children, indirect bilirubin was greatly increased, which subsequently had a toxic effect on the body as a whole. According to laboratory data, bilirubin was increased to 765 µmol / l, while it remained within these limits throughout the child's life.

After some time, colleagues have identified suchsymptoms in older children, but with one feature. Bilirubin was increased only 15 times from the norm and decreased to the norm during life. Toxic effects on the body was not. As a result of such observations, the disease got its current name: Crigler-Nayar syndrome, which was first described by two pediatricians.

Description of the disease

Синдром Криглера-Найяра является генетическим disease. Clinic of the disease is expressed in bright jaundice and severe neurological disorders. Jaundice is detected in the first hours after birth and persists throughout life. Lesions occur equally in both boys and girls. Since jaundice is a manifestation of liver problems, in some patients this organ is enlarged.

Signs of CNS damage occur in infancy,at times in the first days of life. They are expressed in muscular tension, involuntary twitching of the eyes, arching of the back, as well as convulsions. Sick children tend to lag behind in mental and physical development. Two types of this disorder are identified. Crigler – Nayar syndrome type 1 and 2 may have different symptoms.

Type 1 symptoms

Unfortunately, type 1 Criggler-Nayar syndromecharacterized by a progressive course. The first symptoms appear in the first hours of life. The baby becomes more pronounced jaundice of the whites of the eyes and skin, and this is different from the usual postpartum jaundice. It does not go away after a few days, and convulsions, involuntary body and eye movements are added to the symptoms. Over time, one can notice a slowdown in mental development associated with bilirubin encephalopathy.

Indicators of free bilirubin in the analysisrise 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 death in a short time. In exceptional cases, these children live to school age.

Type 2 symptoms

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

Blood biochemical parameters with type 2 are muchbelow - the level of bilirubin is about 200 µmol / l. This indicator suggests that glucuronyltransferase enzyme activity is less than 20% of normal. In bile there is a bilirubin-gluguronid. Diagnosis with "Phenobarbital" positive.

Bilirubin encephalopathy

What is terrible syndrome Kriegler-Nayar?Symptoms of the disease manifest themselves in four phases of brain poisoning. In the first phase, the baby behaves apathetic and very sluggish. This is manifested in poor sucking, a relaxed state, a sharp reaction to extraneous sounds. The baby’s cry is monotonous, he often belches and vomiting may even open, his eyes wandering, as if he has lost something. Breathing can be slow.

The second phase can last from several days toseveral months. The child becomes tense, the muscles of the body assume an unnatural position, the handles are constantly clenched into a fist, and the back is arched. The cry from the monotonous turns into a very sharp, the sucking reflex and the reaction to the sounds disappear. There are cramps, snoring, loss of consciousness.

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

The fourth phase may appear at 5 months of life.and manifest overt symptoms of physical and mental retardation. The kid does not hold his head, does not follow moving objects, does not react to the voice of close people. He develops convulsions, paresis, paralysis. Unfortunately, the brain poisoning in type 1 occurs very quickly, and the child dies in infancy.

Causes of the disease

The main cause of the disease lies in the genes.They disrupt the formation of a certain enzyme, which is responsible for the production of bilirubin. For the most part, the Asian population suffers from this disease. The mutated gene is transmitted in an autosomal recessive manner. In this case, both parents of the baby can be carriers of the mutation, but be healthy themselves. It can also be the carrier of one of the parents, then the probability of manifestation of the disease will be 50 to 50%.

Hereditary gene mutation leads to the fact thatthe body is unable 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 does not function in newborn children. The brain of a child is exposed to poisoning, where toxic bilirubin accumulates.

Treatment

For children diagnosed with syndromeCrigler-Nayar, treatment is aimed at removing free bilirubin from the body. It is also important to prevent the development of toxic brain damage.

Для его лечения используются лекарства, increase the activity of uridine diphosphate glucuronidase, an enzyme that leads to irreversible processes in the liver. To do this, apply "Phenobarbital" in a dosage of up to 5 mg per kilogram of body weight per day. It should be noted that it has a positive effect exclusively on type 2 Criggler-Nayar syndrome. With type 1, the organism practically does not react to "Phenobarbital".

For both types of illness, sessions are held.phototherapy, plasma is injected, exchange transfusions are performed. All procedures are prepared to perform a liver transplant - for children with type 1, this is the only chance to survive.

Diagnostics

Today, medicine is able to establishcauses of diseases such as Crigler-Nayar 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 the genetic predisposition to diseases even in utero. After the birth of a baby, DNA diagnostics gives an accurate answer about whether there is a mutation in certain genes.

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

If there is a suspicion of Krigler-Nayyar syndrome, an anamnesis is collected from parents and DNA tests are performed to confirm the diagnosis.

Prevention of disease

Preventive measures for Crigler-Nayar syndrome are to prevent the occurrence of complications.

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

In type II syndrome, prevention is reduced toinforming the patient about the circumstances that may provoke an exacerbation of the disease. These are complicating infections, overstrain, pregnancy, taking alcohol and drugs 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 the Crigler-Nayar syndrome (treatment, causes, symptoms of which are examined by us) can manifest itself in children individually.