Kriegler-Nayyar Syndrome: Causes, Symptoms, Diagnosis, Treatment

At the heart of the Kriegler-Nayar syndrome (nonhemolytic nuclear jaundice) is the complete absence in the hepatocytes of the enzyme glucuronyltransferase and the absolute inability of the liver to conjugate bilirubin (microsomal jaundice). In connection with this, the content of unconjugated bilirubin in the blood sharply rises and it exerts a toxic effect on the central nervous system, the subcortical nodes (nuclear jaundice) are affected. There are also significant dystrophic changes in the myocardium, skeletal muscles and other organs, as a manifestation of the toxic effects of bilirubin. When examining liver biopsy specimens, as a rule, there are no morphological changes, sometimes there is a small fatty hepatosis, a slight periportal fibrosis.

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Symptoms of Kriegler-Nayar Syndrome

There are two types of Kriegler-Nayyar syndrome:

I type of Kriegler-Nayyar syndrome is characterized by the following features:

• transmitted autosomal recessive;
• intensive jaundice develops during the first days after birth and lasts a lifetime;
• the CNS lesion appears already in infancy and manifests as tonic or juvenile convulsions, opisthotonus, athetosis, nystagmus, muscle hypertension, lag in physical and mental development;
• there is severe hyperbilirubinemia (the level of unconjugated bilirubin is increased 10-50 times compared to the norm);
• in bile only traces of bilirubin are found;
• bilirubinuria is absent, the number of urobilin bodies in the urine and feces is small; Acholia of feces is possible;
• Phenobarbital does not reduce the content of unconjugated bilirubin in the blood;
• possibly a slight increase in the activity in the blood of enzymes that reflect the function of the liver (alanine aminotransferase, fructose-1-phosphataldolase);
• most patients die in the first year of life.

II type of Kriegler-Nayar syndrome has the following characteristic manifestations:

• transmitted autosomal dominant type;
• the course of the disease is more benign;
• jaundice is less intense;
• the content of unconjugated bilirubin in serum is 5-20 times higher than the norm;
• Neurological disorders are rare and mild, may be absent altogether;
• bile is colored, a significant amount of urobilinogen is detected in the stool;
• bilirubinuria is absent;
• the use of phenobarbital leads to a decrease in serum bilirubin.

It is not always easy to distinguish types 1 and 2 of the Kriegler-Nayar syndrome. To differentiate them it is possible, having estimated efficiency of treatment by phenobarbital by definition of fractions of bilirubin by means of high-performance liquid chromatography. In addition, these types can be distinguished by determining the content of bile yellow pigments after the administration of phenobarbital. At type 2, the serum bilirubin level and the proportion of unconjugated bilirubin decrease, and the mono- and diconjugate content in the bile increases. At type 1, the serum bilirubin level does not decrease, and in bile mainly unconjugated bilirubin is detected. Apparently, in the future, the diagnosis will be based on in vitro expression of the mutant DNA of patients.

The Kriegler-Nayar syndrome must be differentiated from the physiological jaundice of the newborns, which is due to the insufficient maturity of the liver's conjugation system at the time of the birth of the child. This jaundice has the following characteristic features that distinguish it from the Kriegler-Nayar syndrome:

• jaundice appears on the second-third day of life, reaches a maximum by the fifth day and passes without treatment for 7-10 days in term-born and 10-14 days-in premature infants;
• the content of unconjugated bilirubin in the blood serum does not exceed 170 μmol / l for those born on time and 250 μmol / L for premature infants;
• no lesions of the central nervous system are observed.