The Krigler-Nayyar Syndrome

A distinctive feature of congenital non-hemolytic unconjugated hyperbilirubinemia, described and named after the authors of Kriegler-Nayyar in 1952, is a high level of free bilirubin fraction in the blood in the complete absence of conjugated( bound) bilirubin. Later, lighter forms of pathology were described. With a complete defect in the glucuronyl-transferase system, the feces of patients with normal color, urine contains urobilin, while bile is often colorless, it lacks bilirubin. As a result of early hyperbilirubinemia, clinically manifested by severe jaundice that persists throughout the life of the patient, and a moderate increase in liver size( hepatomegaly), classical bilirubin encephalopathy develops. Most patients die, with a pathological anatomical study find nuclear jaundice, and few survivors suffer from choreoathetosis.

Both for diagnosis and for treatment, the key is the ability to suppress the activity of the enzyme UDP-glucuronyltransferase with phenobarbital. This is impossible with a complete defect( type I of Kriegler-Nayyar syndrome), although other functional liver tests are normal, including results of the study of bilirubin metabolism, hepatic accumulation absorption. The gallbladder is well revealed in cholecystography. In another variant of pathology( type II), the level of unconjugated( unbound) bilirubin is slightly elevated. Under the influence of phenobarbital, the ability of patients to conjugate bilirubin increases, the introduction of the drug for 2-3 weeks can reduce the concentration of bilirubin in the plasma. Thus, the reaction to phenobarbital is the best both diagnostic and drug test for distinguishing the two forms of the Kriegler-Nayar syndrome, which is inherited autosomally-recessively with a full enzyme block, and in cases with an incomplete defect, the transmission is autosomal dominant with incomplete expression( penetranceand expression).

This defect is not always easy to distinguish from physiological jaundice of newborns. The difference between Kriegler-Nayar syndrome and biliary atresia and congenital hepatitis is an increase in the level of conjugated bilirubin with a complicated outflow of bile and the presence of signs of damage to hepatocytes. In addition, in all cases, a disease such as hypothyroidism should be excluded as the cause of an elevated bilirubin( hyperbilirubinemia).

As a rule, this disease is severe, in most cases it ends with a lethal outcome as a result of the development of nuclear jaundice or the attachment of other diseases. The forecast is directly conditioned by the effectiveness of measures aimed at preventing nuclear jaundice.

In cases where it is not possible to maintain the serum bilirubin level below 340 μmol / l with the help of different therapies( phototherapy and blood transfusion), phenobarbital is prescribed at 5-8 mg / kg of body weight per day for 2-3 weeks undercontrolling the level of bilirubin. Given the greatest sensitivity of the nervous system during this period of brain growth, as well as the stages of its functional maturation to the toxic effect of bilirubin, together with the use of phenobarbital, phototherapy is recommended, despite the fact that the latter makes it difficult to formulate and correctly evaluate a pharmacological test. Nevertheless, the delay in diagnosing is considered very justified, since it is about the integrity and normal functioning of the brain. With prolonged treatment with phenobarbital, additional administration of vitamin D preparations is shown. In the absence of enzyme( UDF-glucuronyltransferase), as well as the absence of positive results of phenobarbital therapy in patients with children with the help of phototherapy and replacement blood transfusion, the level of bilirubin can be kept within 70-140 μmol / l, which helps to protect the brain from the toxic effects of bilirubin. If after the first months of life for a period of several years to systematically perform phototherapy for 12 hours daily, the concentration of bilirubin is maintained within fairly acceptable limits( 170-290 μmol / L), which is compatible with the normal development of the child.