Quite rarely, one can hear about a disease such as Krigler-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 look at what this disease is and what treatment is in this case.
Discovery story
I must say that they discovered this syndrome quite recently, in 1952 of the last century. Two pediatricians, Kriegler and Nayyar, watching newborn children, for the first time described unusual symptoms of jaundice. Further research 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 studies, bilirubin was increased to 765 μmol / L, while it remained within these limits throughout the life of the child.
After some time, colleagues revealed similar symptoms in older children, but with one peculiarity. Bilirubin was increased only 15 times from the norm and during life decreased to normal. There was no toxic effect on the body. As a result of such observations, the disease got its current name: Krigler-Nayyar syndrome, a description of which was first made by two pediatricians.
Description of the disease
Krigler-Nayyar syndrome is a genetic disease. The 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 are found to the same extent in both boys and girls. Since jaundice is a manifestation of liver problems, in some patients this organ is enlarged.
Signs of central nervous system damage occur in infancy, sometimes in the early days of life. They are expressed in muscle tension, involuntary twitching of the eyes, arching of the back, as well as cramps. Sick children, as a rule, lag behind in mental and physical development. Two types of this disorder come to light. Kriegler-Nayyar syndrome type 1 and 2 can have various symptoms.
Symptoms of type 1
Unfortunately, Kriegler-Nayyar syndrome type 1 is characterized 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 differs from ordinary postpartum jaundice. It does not go away after a few days, and cramps, involuntary movements of the body and eyes are added to the symptoms. Over time, you can notice a slowdown in mental development associated with bilirubin encephalopathy.
The parameters of free bilirubin in the analyzes increase to 324-528 μmol / L, in fact, it is 15-50 times higher than the norm. Intoxication of the brain in this case leads to death in a short time. In exceptional cases, such children live to school age.
Symptoms of type 2
The first signs of the disease appear much later than with type 1. The disease can manifest itself in the first years of life. In some children, jaundice does not occur until adolescence, and neurological abnormalities are rare. Symptoms are similar to type 1, but not so severe. Bilirubin encephalopathy can occur after infection or severe stress.
The biochemical parameters of blood with type 2 are much lower - the level of bilirubin is about 200 μmol / l. This indicator suggests that the activity of the glucuronyl transferase enzyme is less than 20% of normal. In bile, there is bilirubin-gluguronide. Diagnosis with Phenobarbital is positive.
Bilirubin encephalopathy
Why is Kriegler-Nayyar Syndrome terrible? Symptoms of the disease manifest in brain poisoning in four phases. In the first phase, the baby is apathetic and very sluggish. This is manifested in poor sucking, a relaxed state, a sharp reaction to extraneous sounds. The cry of the baby is monotonous, he often spits up and may even vomit, his gaze wandering, as if he had lost something. Breathing may be slow.
The second phase can last from several days to several months. The child becomes tense, the muscles of the body take an unnatural position, the arms are constantly clenched into a fist, the back is arched. A cry from monotonous turns into a very sharp one, the sucking reflex and reaction to sounds disappear. Convulsions, snoring, loss of consciousness appear.
The third phase is manifested by a period of false improvement. All previous symptoms temporarily disappear.
The fourth phase can appear at 5 months of life and manifest itself as obvious symptoms of physical and mental retardation. The kid does not hold his head, does not follow moving objects, does not respond to the voice of loved ones. He develops cramps, paresis, paralysis. Unfortunately, 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 of the planet suffers from this disease. The mutating 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. One of the parents can also be a carrier, then the probability of the manifestation of the disease will be 50 to 50%.
The hereditary mutation of the gene leads to the fact that the 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 newborns does not function. The brain of the child is poisoned, where toxic bilirubin accumulates.
Treatment
For children who are diagnosed with Krigler-Nayyar syndrome, treatment is aimed at removing free bilirubin from the body. It is also important to prevent the development of toxic brain damage.
For its treatment, drugs are used that increase the activity of uridine diphosphate glucuronidase, an enzyme that leads to irreversible processes in the liver. For this, Phenobarbital is used in a dosage of up to 5 mg per kilogram of weight per day. It should be noted that it positively affects exclusively Krigler-Nayyar type 2 syndrome. With type 1, the body practically does not respond to Phenobarbital.
With both types of the disease, phototherapy sessions are carried out, plasma is injected, exchange blood transfusions are performed. All procedures are prepared to perform liver transplantation - for children with type 1 this is the only chance to survive.
Diagnostics
Today, medicine is able to establish the causes of diseases such as Krigler-Nayyar syndrome. Symptoms and treatment methods have been described for a long time, and now, with the help of DNA tests, you can determine the genetic predisposition to diseases even in utero. After the birth of the baby, DNA diagnostics give an accurate answer about whether there is a mutation in certain genes.
Also, with developing jaundice, a test with "Phenobarbital" is done. The result of the analysis shows the type of disease.
If there is a suspicion of Krigler-Nayyar syndrome, an anamnesis is collected from the parents and DNA tests are performed to confirm the diagnosis.
Disease prevention
Preventive measures for Kriegler-Nayyar syndrome are to prevent complications.
In type I syndrome, it is very important to prevent the development of bilirubin encephalopathy, because it is it that leads to premature death of the patient.
In type II syndrome, prevention comes down to informing the patient about circumstances that can trigger an exacerbation of the disease. These are complicating infections, overstrain, pregnancy, taking alcohol and drugs without the supervision of a doctor. 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 Krigler-Nayyar syndrome (treatment, causes, symptoms of which we examined) can occur individually in children.