Crigler-Najjar syndrome

Crigler-Najjar syndrome

Crigler-Najjar syndrome is a hereditary disease characterized by high levels of indirect bilirubin in the blood. This syndrome is a condition that is passed down from parents to children. 

Bilirubin is a yellow pigment in the blood, which is formed when red blood cells are broken down naturally. The first bilirubin formed after the breakdown of blood cells is indirect bilirubin. Indirect bilirubin will enter the liver (liver) to be converted into direct bilirubin, so that it can be removed through urine and feces.

Crigler-Najjar syndrome causes indirect bilirubin to accumulate in the blood and cause jaundice. If not treated, this condition can cause complications in the form of kernicterus which can be fatal.

Causes of Crigler-Najjar Syndrome

Crigler-Najjar syndrome is caused by a mutation in the UGT1A1 gene that produces the UGT bilirubin enzyme. UGT bilirubin enzyme works to convert indirect bilirubin into direct bilirubin. Mutations in the UGT1A1 gene can cause a decrease in the function of the enzyme.

Based on the remaining UGT bilirubin enzyme function, Crigler-Najjar syndrome is divided into two types, namely:

  • Crigler-Najjar syndrome type 1, which occurs when the UGT bilirubin enzyme is inactive or does not work at all
  • Crigler-Najjar syndrome type 2 or Arias syndrome, which occurs when the enzyme still works, but decreases until only about 20% remains

The two conditions above cause indirect bilirubin to be unable to be converted into direct bilirubin. As a result, bilirubin is difficult to dissolve in water and cannot be removed by the body so this condition causes indirect bilirubin to accumulate in the blood and cause jaundice .

Crigler-Najjar syndrome is an autosomal recessive disease. In other words, a person can suffer from this disease if the UGT1A1 gene mutation occurs in both parents. Whereas if it is only inherited from one of the parents, the mutation of the UGT1A1 gene can cause Gilbert's syndrome , which is a milder condition than Crigler-Najjar syndrome.

Symptoms of Crigler-Najjar Syndrome

Symptoms that appear in Crigler-Najjar syndrome sufferers include:

  • Jaundice, which appears a few days after birth and worsens over time
  • Bewildered
  • Mental changes and thinking ability
  • Lethargy or the body feels very tired
  • Decreased consciousness
  • No appetite
  • Vomiting

When should you go to the doctor?

Do a genetic consultation and examination when planning a pregnancy, especially if there is a history of Crigler-Najjar syndrome in your family or your partner. The purpose is to detect the possibility of Crigler-Najjar syndrome being transmitted to the fetus.

Check with a doctor if you or your baby has jaundice that does not heal. This can indicate Crigler-Najjar syndrome.

Diagnosis of Crigler-Najjar Syndrome

The doctor will ask questions related to the symptoms experienced and the patient's health history, followed by a physical examination. Further to confirm the diagnosis, the doctor will carry out a number of the following examinations:

  • Measurement of bilirubin level
    Measurement of bilirubin level is done by examining the patient's blood sample. In Crigler-Najjar syndrome type 1, bilirubin levels are in the range of 20–50 mg/dL. While the bilirubin level in Crigler-Najjar syndrome type 2 ranges between 7-20 mg/dL.
  • Liver
    function test In patients with Crigler-Najjar syndrome, the levels of liver enzymes checked during the liver function test are generally within the normal range. However, in some cases, liver enzyme levels can increase due to cholestasis, which is the blockage of bile flow in the liver.
  • Liver biopsy
    examination In this examination, tissue samples from the liver will be taken and then examined under a microscope.

Treatment of Crigler-Najjar Syndrome

The treatment of Crigler-Najjar syndrome depends on the type that is suffered. Here is the explanation:

Treatment of Crigler-Najjar syndrome type 1

The first step in the treatment of Crigler-Najjar syndrome type 1 is to prevent the occurrence of kernicterus, which can be done with the following methods:

  • Blue light phototherapy, to break down bilirubin so that it can be more easily excreted through urine
  • Administration of calcium phosphate tablets, to help remove bilirubin
  • Exchange transfusion, for the baby's blood with blood from a donor until the bilirubin level returns to normal
  • Liver transplantation or replacing a damaged liver with a liver from a donor, to prevent complications.

Treatment of Crigler-Najjar syndrome type 2

Patients with Crigler-Najjar syndrome type 2 can improve on their own without having to be treated. However, doctors can give phenobarbital to lower bilirubin levels by 30%, in 2-3 weeks. In rare cases, some patients with Crigler-Najjar syndrome type 2 also require exchange transfusion and phototherapy.

Complications of Crigler-Najjar Syndrome

In severe conditions, Crigler-Najjar syndrome type 1 can cause prolonged jaundice from infancy to adulthood. This condition requires continuous handling, because if not handled, death in childhood can occur.

In addition, sufferers of Crigler-Najjar syndrome type 1 who can survive to adulthood are at risk of kernicterus . The life expectancy of patients with this type of Crigler-Najjar syndrome is usually around 30 years.

Prevention of Crigler-Najjar Syndrome

To prevent Crigler-Najjar syndrome, do counseling and genetic testing before planning a pregnancy. That way, it can be known if there is a risk of Crigler-Najjar syndrome going down to the fetus.

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