Crigler-Najjar syndrome

Crigler–Najjar syndrome is a very rare congenital genetic disorder involving impaired metabolism of a compound known as bilirubin and is therefore closely related to the problem of jaundice.

Causes

The cause is a mutation in a gene important for the enzyme UDP‑glucuronyltransferase. Bilirubin, as described in more detail in texts on jaundice, is a compound continuously produced in the body as a product of the breakdown of the blood pigment hemoglobin. Bilirubin is then transported to the liver, where it undergoes conjugation. This crucial reaction is carried out by the enzyme UDP‑glucuronyltransferase, and the resulting conjugated bilirubin can be excreted into bile and subsequently enters the intestine. Impairment of enzyme function leads to defective conjugation and inability to excrete bilirubin from the body via bile.

Symptoms

Two types of the syndrome are distinguished based on the severity of impairment. Crigler–Najjar type I leads to complete absence of enzyme activity, whereas in type II partial enzyme function is preserved. It logically follows that type I is more dangerous and associated with more severe manifestations.

The disorder presents in the neonatal period with severe jaundice (not to be confused with common neonatal jaundice). Unconjugated bilirubin accumulates in the body and, in children, can cross the blood–brain barrier (unlike in adults), causing severe and irreversible brain damage (kernicterus). Brain damage may lead to death or result in severe disabilities, including intellectual impairment, various motor disorders, learning and attention disorders, and others. It should be noted that brain damage is less common in type II.

Diagnosis

Affected individuals show very high levels of unconjugated bilirubin. However, a definitive diagnosis can only be established through genetic testing.

Treatment

Prevention of this congenital disorder is not possible under current medical conditions. Treatment includes classic phototherapy (irradiation with blue light, which breaks down unconjugated bilirubin into harmless compounds), which is also used in the treatment of common neonatal jaundice.

In type II, phenobarbital is administered to improve the function of the UDP‑glucuronyltransferase enzyme. Before the introduction of phototherapy, type I was fatal. Today, with maximal therapy, patients with Crigler–Najjar syndrome type I may survive to 30–40 years of age.

• ťažká žltačka u novorenca
• hromadenie nekonjugovaného bilirubínu v tele (u detí preniká do mozgu)
• narušenie intelektu
• rôzne poruchy hybnosti
• poruchy učenia a pozornosti