Crigler–Najjar syndrome

Diagram of bilirubin metabolism

Crigler–Najjar syndrome is a rare genetic disorder characterized by a severe form of hyperbilirubinemia due to a deficiency in the enzyme UDP-glucuronosyltransferase (UGT1A1). This enzyme is crucial for the conjugation and subsequent excretion of bilirubin, a byproduct of hemoglobin breakdown. The syndrome is named after Dr. John Fielding Crigler and Dr. Victor Assad Najjar, who first described the condition in 1952.

Pathophysiology

Crigler–Najjar syndrome results from mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation. This results in the accumulation of unconjugated bilirubin in the blood, causing jaundice and potentially leading to kernicterus, a form of brain damage.

Types

Crigler–Najjar syndrome is classified into two types:

Type I

Type I is the more severe form, characterized by a complete absence of UGT1A1 activity. Patients with Type I Crigler–Najjar syndrome have very high levels of unconjugated bilirubin and are at significant risk for kernicterus. This type does not respond to phenobarbital treatment.

Type II

Type II, also known as Arias syndrome, is less severe and results from partial UGT1A1 activity. Patients with Type II have lower levels of bilirubin and a reduced risk of kernicterus. This type often responds to phenobarbital, which can induce enzyme activity and lower bilirubin levels.

Clinical Presentation

The primary symptom of Crigler–Najjar syndrome is persistent jaundice, which is evident shortly after birth. In Type I, jaundice is severe and persistent, while in Type II, it may be milder.

Diagnosis

Diagnosis is based on clinical presentation, family history, and laboratory tests showing elevated levels of unconjugated bilirubin. Genetic testing can confirm mutations in the UGT1A1 gene.

Treatment

Type I

Management of Type I Crigler–Najjar syndrome includes aggressive phototherapy to reduce bilirubin levels and prevent kernicterus. Liver transplantation may be considered as a definitive treatment.

Type II

Type II can often be managed with phenobarbital, which helps to induce residual UGT1A1 activity and lower bilirubin levels.

Prognosis

The prognosis for Crigler–Najjar syndrome varies depending on the type. Type I has a high risk of neurological damage if not managed effectively, while Type II generally has a better prognosis with appropriate treatment.

Related pages

• Jaundice
• Kernicterus
• UDP-glucuronosyltransferase
• Hyperbilirubinemia