It is quite rare to hear about such a disease as Crigler-Najjar syndrome. But, unfortunately, this diagnosis can be made to 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 is the treatment in this case.
Discovery history
It must be said that this syndrome was discovered quite recently, in 1952 of the last century. Two pediatricians, Kriegler and Nayyar, observing newborn babies, first described the 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 tests, bilirubin was increased to 765 µmol/L, while it remained within these limits throughout the life of the child.
After a while, colleagues found similar symptoms in older childrenage, but with one feature. Bilirubin was only 15 times higher than normal and decreased to normal throughout life. There was no toxic effect on the body. As a result of these observations, the disease received its current name: Crigler-Najjar syndrome, which was first described by two pediatricians.
Description of disease
Crigler-Najjar Syndrome is a genetic disorder. 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. The 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, sometimes 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. Crigler-Najjar syndrome types 1 and 2 may have different symptoms.
Type 1 symptoms
Unfortunately, type 1 Crigler-Najjar syndrome 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 the usual postpartum jaundice. It does not go away after a few days, and convulsions are added to the symptoms,involuntary movements of the body and eyes. Over time, mental retardation associated with bilirubin encephalopathy can be noticed.
Indicators of free bilirubin during 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 within a short time. In exceptional cases, these children survive to school age.
Type 2 symptoms
The first signs of the disease appear much later than with type 1. The disease can manifest itself in the first years of life. Some children do not develop jaundice until adolescence, and neurological abnormalities are rare. Symptoms are similar to type 1, but not as severe. Bilirubin encephalopathy can occur after an infection or severe stress.
Biochemical parameters of blood in type 2 are much lower - the level of bilirubin is about 200 µmol/l. This indicator indicates that the activity of the glucuronyl transferase enzyme is less than 20% of the norm. Bile contains bilirubin-gluguronide. Diagnosis with Phenobarbital is positive.
Bilirubin encephalopathy
What is so terrible about Crigler-Najjar syndrome? The symptoms of the disease are manifested in the poisoning of the brain in four phases. In the first phase, the baby behaves apathetically and very sluggishly. This is manifested in poor sucking, a relaxed state, a sharp reaction to extraneous sounds. At the same time, the cry of the baby is monotonous, heoften spit up and may even vomit, his eyes are 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 on an unnatural position, the arms are constantly clenched into a fist, the back arches. The cry from monotonous turns into a very sharp one, the sucking reflex and the reaction to sounds disappear. There are convulsions, snoring, loss of consciousness.
The third phase is manifested by a period of false improvement in the state. All previous symptoms temporarily disappear.
The fourth phase may appear at 5 months of age and manifest clear symptoms of physical and mental retardation. The baby does not hold his head, does not follow moving objects, does not respond to the voice of loved ones. He develops convulsions, paresis, paralysis. Unfortunately, type 1 brain poisoning occurs very quickly, and the child dies in infancy.
Causes of 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, this disease affects the Asian population of the planet. 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 he althy themselves. One of the parents can also be a carrier, then the probability of the manifestation of the disease will be 50 to 50%.
Hereditary gene mutation leads tothe 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 does not function in newborns. The child's brain is poisoned, where toxic bilirubin accumulates.
Treatment
For children diagnosed with Crigler-Najjar syndrome, treatment aims to remove free bilirubin from the body. It is also important to prevent the development of toxic brain damage.
To treat it, 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 at a dosage of up to 5 mg per kilogram of body weight per day. It should be noted that it has a positive effect only on Crigler-Najjar type 2 syndrome. With type 1, the body practically does not react to Phenobarbital.
For both types of disease, phototherapy sessions are performed, plasma is injected, and exchange transfusions are performed. All procedures prepare to perform a liver transplant - for children with type 1, this is the only chance to survive.
Diagnosis
Today, medicine is able to establish the causes of diseases such as Crigler-Najjar syndrome. Symptoms and treatments 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 baby is born, DNA diagnostics gives 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.
When Crigler-Najjar syndrome is suspected, a history is taken from the parents and DNA tests are done to confirm the diagnosis.
Disease prevention
Preventive measures for Crigler-Najjar 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 leads to premature death of the patient.
In type II syndrome, prevention comes down to informing the patient about the circumstances that can provoke an exacerbation of the disease. These are complicating infections, overexertion, 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. It is impossible to describe all cases in this article, because Crigler-Najjar syndrome (treatment, causes, symptoms of which we have considered) can manifest itself in children individually.
