Crigler–Najjar syndrome

Crigler–Najjar syndrome
ICD-10	E80.5
ICD-9	277.4
DiseasesDB	3176
MedlinePlus	001127
eMedicine	med 476
MeSH ID	D003414

Crigler–Najjar syndrome (CNS) is a rare genetic disorder affecting bilirubin metabolism, resulting in non-hemolytic jaundice. It leads to high levels of unconjugated bilirubin, posing a risk of brain damage in infants.

CNS is classified into type I and type II, also known as Arias syndrome. These conditions, along with Gilbert's syndrome, Dubin–Johnson syndrome, and Rotor syndrome, comprise the hereditary defects in bilirubin metabolism. CNS is significantly rarer than Gilbert's syndrome, with only a few hundred cases documented.

Type I

Type I Crigler–Najjar syndrome is extremely rare, with consanguinity being a risk factor. It follows an autosomal recessive inheritance pattern. Symptoms include persistent, intense jaundice from the first days of life, with serum bilirubin levels typically above 345 µmol/L, far exceeding the normal range of 2–14 μmol/L. In these patients, the enzyme UGT1A1 is not expressed in the liver, making them unresponsive to phenobarbital treatment, which induces the Cytochrome P450 enzymes. The lack of enzyme activity leads to a severe conjugation defect, particularly affecting bilirubin.

Before the advent of phototherapy, affected children often succumbed to kernicterus or suffered significant neurological damage if they survived into early adulthood. Current treatments include exchange transfusions, prolonged daily phototherapy, the use of heme oxygenase inhibitors, oral calcium phosphate and carbonate to bind bilirubin in the intestines, and liver transplantation before brain damage occurs or phototherapy loses its effectiveness.

Type II

Type II is differentiated from Type I by lower serum bilirubin levels, pigmented bile, and detectable but reduced UGT1A1 enzyme activity. Treatment with phenobarbital, which can decrease serum bilirubin by at least 25%, helps distinguish Type II from Type I. Type II's inheritance pattern is generally considered autosomal recessive.

Differential Diagnosis

Conditions such as neonatal jaundice and various liver diseases can mimic CNS symptoms. Unconjugated hyperbilirubinemia can be due to increased bilirubin production, decreased clearance, or liver dysfunction. In CNS and Gilbert syndrome, routine liver function tests appear normal, with no evidence of hemolysis.

Research

Research into Crigler–Najjar syndrome includes successful hepatocyte transplantation in a 10-year-old girl with Type I and gene therapy investigations using the Gunn rat model, an animal lacking the enzyme uridine diphosphate glucuronyltransferase, mirroring CNS pathology.

Eponym

The syndrome is named after American Pediatrician John Fielding Crigler and Lebanese-American Pediatrician Victor Assad Najjar, who first described it.

See also

• Dubin–Johnson syndrome
• Gilbert's syndrome
• Rotor syndrome
• Hemolysis
• Jaundice
• Liver transplantation
• Phototherapy

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