Crigler-Najjar Syndrome: Symptoms, Causes, Treatment

What are the symptoms of Crigler-Najjar syndrome?

Crigler-Najjar syndrome is a rare genetic disorder characterized by elevated levels of bilirubin in the blood, which can lead to jaundice and potentially serious complications. There are two types of Crigler-Najjar syndrome: type 1 and type 2.

Type 1 is more severe and presents early in life, often in the first few days after birth. Symptoms of type 1 Crigler-Najjar syndrome may include:

1. Severe jaundice: Yellowing of the skin and whites of the eyes (icterus) due to high levels of bilirubin in the blood.
2. Neurological symptoms: In severe cases, elevated bilirubin levels can lead to neurological problems such as muscle stiffness, poor feeding, lethargy, and in some cases, seizures or brain damage (kernicterus).
3. Failure to thrive: Poor weight gain and growth in infancy.
4. Developmental delays: Due to the potential effects of high bilirubin levels on the brain.
5. Other signs: These may include a high-pitched cry, arching of the back, and irritability.

Type 2 Crigler-Najjar syndrome is less severe and usually presents later in childhood or adolescence. Symptoms of type 2 Crigler-Najjar syndrome are similar to those of type 1 but are typically milder. The jaundice may come and go, and neurological symptoms are less common.

It’s important to note that Crigler-Najjar syndrome is a serious condition that requires ongoing medical management. If you or your child are experiencing symptoms of Crigler-Najjar syndrome, it’s essential to seek medical attention for a proper diagnosis and management plan.

What are the causes of Crigler-Najjar syndrome?

Crigler-Najjar syndrome is a genetic disorder caused by mutations in the UGT1A1 gene, which provides instructions for making an enzyme called uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). This enzyme is responsible for converting bilirubin, a waste product produced by the normal breakdown of red blood cells, into a form that can be easily excreted from the body.

Mutations in the UGT1A1 gene result in reduced or absent activity of the UGT1A1 enzyme, leading to impaired bilirubin metabolism. As a result, bilirubin levels in the blood become elevated, leading to the symptoms of Crigler-Najjar syndrome, such as jaundice.

Crigler-Najjar syndrome is inherited in an autosomal recessive pattern, which means that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder. If both parents carry a mutation in the UGT1A1 gene, each of their children has a 25% chance of inheriting two mutated copies of the gene and developing Crigler-Najjar syndrome.

What is the treatment for Crigler-Najjar syndrome?

The treatment for Crigler-Najjar syndrome aims to reduce bilirubin levels in the blood to prevent the complications associated with high bilirubin levels, such as kernicterus (brain damage). The primary treatment options include:

1. Phototherapy: This is the most common treatment for Crigler-Najjar syndrome. Phototherapy involves exposing the skin to a special type of light that helps convert bilirubin into a form that can be excreted from the body more easily. Phototherapy is usually done at home using a phototherapy device, and it needs to be continued for several hours each day, often for life.
2. Liver transplantation: In severe cases of Crigler-Najjar syndrome that do not respond to phototherapy, a liver transplant may be considered. A liver transplant can provide a source of UGT1A1 enzyme-producing cells that can metabolize bilirubin normally. However, liver transplantation is a major surgery with risks and complications, and it is usually reserved for individuals with severe symptoms or complications of the disease.
3. Medications: Some medications, such as phenobarbital, may be used to help reduce bilirubin levels in people with Crigler-Najjar syndrome. Phenobarbital can increase the activity of the UGT1A1 enzyme, helping to improve bilirubin metabolism. However, not all individuals with Crigler-Najjar syndrome respond to phenobarbital, and it may not be effective in all cases.
4. Monitoring and support: Regular monitoring of bilirubin levels and liver function is important for individuals with Crigler-Najjar syndrome. Supportive care, including nutritional support and management of any complications, is also important for overall health and well-being.

It’s important for individuals with Crigler-Najjar syndrome to work closely with a healthcare team experienced in managing the condition to develop an appropriate treatment plan based on their specific needs and circumstances.