Crigler-Najjar syndrome type 2 is a severe condition that causes elevated levels of bilirubin in the blood (hyperbilirubinemia). Bilirubin normally is produced by the body when old red blood cells are broken down. However, people with CN-2 develop hyperbilirubinemia even when red blood cells are not excessively broken down, because they have too little of a liver enzyme needed for conversion and excretion of bilirubin.
Symptoms of Crigler-Najjar syndrome type 2
The main symptom of CN-2 is persistent jaundice, which is yellowing of the skin, mucous membranes and whites of the eyes. This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO).
|Medical Terms||Other Names||Learn More:HPO ID|
|80%-99% of people have these symptoms|
|Prolonged neonatal jaundice||Prolonged yellowing of skin in newborn||0006579|
|Percent of people who have these symptoms is not available through HPO|
|Autosomal recessive inheritance||0000007|
|Jaundice||Yellow skinYellowing of the skin||0000952|
Crigler-Najjar syndrome is caused by mutations in the UGT1A1 gene. This gene provides instructions for creating bilirubin-UGT enzyme that play a critical role in many functions of the body. The bilirubin-UGT enzyme performs a chemical reaction which makes bilirubin dissolvable in water so that it can be removed from the body.
Mutations in the UGT1A1 gene that cause Crigler-Najjar syndrome result in reduced or absent function of the bilirubin-UGT enzyme. People with CN1 have no enzyme function, while people with CN2 have less than 20 percent of normal function.
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. Diagnosis is based on biochemical findings with total serum bilirubin ranging from 6 to 20 mg/dL and presence of bilirubin glucuronides in bile.
Diagnosis is confirmed by genomic DNA analysis (ruling out the need for liver biopsy). It may also help in differentiating between the two types of CNS. Liver biopsy, when it was performed, revealed residual enzymatic activity.
Differential diagnosis includes disorders of excessive bilirubin production (hemolysis). CNS2 can be differentiated from CNS1 by the response to phenobarbital treatment and from mild hepatic deficiency of UGT1A1 (Gilbert syndrome).
Prenatal diagnosis is possible provided both disease-causing mutations have been identified in the proband.