Crigler-Najjar Syndrome: Causes, Symptoms, Treatment, and Cost

Due to a defect in the enzyme that breaks down bilirubin, Crigler-Najjar syndrome is a rare hereditary condition that is characterized by excessive amounts of unconjugated bilirubin in the blood.

Two varieties of Crigler-Najjar syndrome exist:

• Type 1 Crigler-Najjar syndrome: This is the most severe version of the illness, and it is brought on by a total lack of the liver enzyme that conjugates bilirubin. People with type 1 Crigler-Najjar syndrome typically develop symptoms in infancy and require lifelong treatment to prevent bilirubin from accumulating in their blood and causing brain damage.
• Type 2 Crigler-Najjar syndrome: This is a milder form of the condition, and it is caused by a partial deficiency of the enzyme responsible for conjugating bilirubin. People with type 2 Crigler-Najjar syndrome may not develop symptoms until adolescence or adulthood, and they may be able to manage their condition with medications that help lower bilirubin levels.

The major causes of Crigler-Najjar syndrome are :

• Inheritance: Being an autosomal recessive genetic ailment, Crigler-Najjar syndrome requires two copies of the faulty gene to manifest in an individual (one from each parent). A person is termed a carrier if they have just one copy of the gene and typically exhibit no symptoms.
• Genetic mutations: Crigler-Najjar syndrome is caused by mutations in the UGT1A1 gene, which encodes for the enzyme responsible for converting bilirubin into a more water-soluble form.
• Autosomal recessive inheritance: Due to the autosomal recessive nature of the condition's inheritance, both of the kid's parents must be carriers of the mutant gene for the child to be afflicted.
• Absence or deficiency of UGT1A1 enzyme: The genetic mutations result in either the complete absence or significantly reduced levels of the UGT1A1 enzyme, leading to impaired bilirubin metabolism.
• Accumulation of unconjugated bilirubin: Due to the lack or insufficiency of the UGT1A1 enzyme, unconjugated bilirubin accumulates in the body, causing jaundice and other complications.

Some common symptoms of Crigler-Najjar syndrome:

• Jaundice: The most typical sign of Crigler-Najjar syndrome is jaundice. Due to an accumulation of bilirubin in the blood, the skin and eyes become yellow.
• Fatigue: Individuals with Crigler-Najjar syndrome may experience fatigue due to the high levels of bilirubin in their blood, which can affect their energy levels.
• Abdominal pain: Some individuals with Crigler-Najjar syndrome may experience abdominal pain, especially if there is a blockage in the bile ducts due to the buildup of bilirubin.
• Itching: Itching is a common symptom of Crigler-Najjar syndrome, as the buildup of bilirubin in the blood can cause skin irritation.
• Neurological problems: In severe cases of Crigler-Najjar syndrome, high levels of bilirubin in the blood can cause neurological problems, such as seizures or brain damage.

These measures can help you in the prevention of Crigler-Najjar syndrome:

• Genetic counseling: If you have a family history of Crigler-Najjar syndrome, you may want to consider genetic counseling to determine your risk of passing the condition on to your children.
• Regular monitoring: If you or your child has been diagnosed with Crigler-Najjar syndrome, it's important to have regular monitoring of bilirubin levels to ensure they stay within safe limits.
• Avoiding triggers: Certain medications and foods can exacerbate the symptoms of Crigler-Najjar syndrome, so it's important to avoid known triggers and speak with a healthcare provider before starting any new medications or supplements.

These diagnostic tests may be used to confirm a diagnosis of Crigler-Najjar syndrome:

• Bilirubin blood test: This test measures the level of bilirubin in the blood. In individuals with Crigler-Najjar syndrome, bilirubin levels are typically significantly higher than normal.
• Liver function tests: These tests assess the quantities of several proteins and enzymes generated by the liver in the blood. Abnormal levels may indicate liver damage or dysfunction, which can be a symptom of Crigler-Najjar syndrome.
• Genetic testing: This test can identify mutations in the UGT1A1 gene, which is responsible for producing an enzyme that metabolizes bilirubin in the liver. Crigler-Najjar syndrome may arise as a result of gene mutations.
• Phototherapy challenge test: This test involves exposing the skin to specific wavelengths of light to determine if bilirubin levels can be lowered. This test can help to differentiate between Crigler-Najjar syndrome and other conditions that may cause elevated bilirubin levels.
• Liver biopsy: A tiny sample of liver tissue is removed during a liver biopsy for testing. This test can help to identify any liver damage or dysfunction that may be contributing to elevated bilirubin levels.

Crigler-Najjar syndrome can lead to many complications such as:

• Jaundice: One of the primary complications of Crigler-Najjar syndrome is jaundice, which is characterized by the yellowing of the skin and eyes due to the buildup of bilirubin in the bloodstream.
• Kernicterus: The buildup of bilirubin in the brain may sometimes result in kernicterus, a disorder that can harm the brain, induce seizures, and even result in death.
• Liver damage: The constant buildup of bilirubin in the liver can cause damage to the liver cells, leading to liver failure, cirrhosis, and other liver-related complications.
• Fatigue: Many people with Crigler-Najjar syndrome experience fatigue and weakness due to the constant strain on their liver and other organs.
• Infections: Due to their compromised immune systems, people with Crigler-Najjar syndrome are more vulnerable to infections.
• Growth and development issues: Children with Crigler-Najjar syndrome may experience delayed growth and development due to chronic illness.
• Social and emotional issues: Living with a chronic illness can be challenging, and people with Crigler-Najjar syndrome may experience social and emotional issues, such as depression, anxiety, and isolation.
• Treatment complications: Some of the treatments for Crigler-Najjar syndrome, such as phototherapy, can have complications, such as skin irritation, dehydration, and eye damage.

These are some remedies that may be helpful for individuals with Crigler-Najjar syndrome at home:

• Milk thistle: Milk thistle is a popular herbal supplement that is commonly used to support liver health. It includes a substance called silymarin, which may aid to preserve the liver and lower bilirubin levels because of its anti-inflammatory and antioxidant effects.
• Turmeric: Spices with anti-inflammatory and antioxidant qualities include turmeric. It often supports liver function and lowers inflammation in Ayurveda medicine. It may be taken as a supplement or used as a culinary spice.
• Amla: Amla, commonly referred to as Indian gooseberry, is a fruit rich in antioxidants and vitamin C. In Ayurveda medicine, it is often utilized to strengthen liver function and advance general health.
• Kutki: For millennia, the herb kutki has been utilized in Ayurveda medicine to improve liver health and lessen inflammation. It is believed to stimulate the production of bile, which can help reduce bilirubin levels
• Triphala: Triphala is an herbal formula that consists of three fruits - amla, haritaki, and bibhitaki. It is commonly used in Ayurvedic medicine to support liver function and promote overall health.

Here are some general guidelines for foods that can be eaten during Crigler-Najjar syndrome:

• High-carbohydrate foods: Carbohydrates are the body's main source of energy, and people with Crigler-Najjar syndrome may need to eat more carbs to compensate for their limited ability to process fats and proteins. Fruits, vegetables, whole grains, and legumes are excellent sources of carbs.
• Low-fat foods: Since the liver is responsible for producing bile to digest fats, people with Crigler-Najjar syndrome may have difficulty digesting high-fat foods. Lean meat cuts, low-fat dairy items, and less fried or processed meals may all be beneficial choices.
• Plenty of fluids: Dehydration may be avoided and good liver function can be promoted by drinking adequate fluids, particularly water. It's important to avoid alcohol, which can be toxic to the liver.
• Nutrient-rich foods: Consuming a range of meals high in nutrients may improve general health and help avoid deficits. Fruits, vegetables, whole grains, lean protein sources, and healthy fats from nuts and seeds are examples of such foods.
• Regular meals: People with Crigler-Najjar syndrome may need to eat more frequent, smaller meals to help maintain steady blood sugar levels and prevent symptoms like fatigue or weakness.

Below are some things that should not be eaten in Crigler-Najjar syndrome:

• High-fat foods: Foods that are high in fat, such as fried foods or processed meats, can affect liver function and aggravate symptoms.
• Sugar: A high intake of sugar, especially in the form of refined sugars or sugary drinks, can lead to liver issues in people with Crigler-Najjar syndrome.
• Alcohol: Alcohol is processed through the liver, and excessive consumption can cause liver damage and worsen the symptoms of Crigler-Najjar syndrome.

The best treatment for Crigler-Najjar syndrome are:

• Phototherapy: The most typical therapy for Crigler-Najjar syndrome is this one. Blue light is used, which aids in the breakdown of bilirubin in the blood, to expose the skin.This treatment is usually done at home and requires the use of a special light box.
• Liver transplant: A liver transplant may be required for Crigler-Najjar syndrome patients with severe instances. The diseased liver is removed during this procedure, and a donor's healthy liver is placed in its place.
• Gene therapy: This is a brand-new, unproven method of treating Crigler-Najjar syndrome. It involves inserting a normal copy of the UGT1A1 gene into the liver cells of the patient. The enzyme that breaks down bilirubin is created by this gene.
• Liver transplant: A liver transplant is often the last resort treatment for patients with severe forms of Crigler-Najjar syndrome who are not responding to medication. During this procedure, the damaged liver is removed and swapped out with a healthy donor liver. Nevertheless, there aren't many liver donors available, and the treatment is expensive.
• Partial hepatectomy: Partial hepatectomy is another surgical treatment that can be used in patients with Crigler-Najjar syndrome. In this surgery, a part of the liver is removed, leaving only the functioning part behind. This procedure can help reduce the amount of bilirubin in the blood and improve the symptoms of the disease.
• Cholecystectomy: The procedure known as cholecystectomy involves surgically removing the gallbladder, which is in charge of holding the bile generated by the liver. In Crigler-Najjar syndrome patients, the liver produces excess bilirubin, which converts to bile and accumulates in the gallbladder. Removing the gallbladder helps reduce the amount of bilirubin in the blood and prevents further complications.
• Portosystemic shunt: Portosystemic shunt is a surgical procedure that connects the portal vein (which carries blood from the digestive tract to the liver) to the inferior vena cava (which carries blood from the liver to the heart) to reduce the pressure in the portal vein. This surgery can help improve liver function and reduce the symptoms of Crigler-Najjar syndrome.

The best doctor to consult for Crigler-Najjar syndrome treatment are :

• Geneticists: This is a genetic disorder and therefore, the primary care provider or family doctor will likely refer the patient to a genetic counselor or a geneticist.
• Hepatologists: This disease affects the liver and can lead to chronic liver disease or cirrhosis, so it's important to see a hepatologist who specializes in liver diseases.
• Pediatricians or neonatologists: If the condition is diagnosed in infants, pediatricians or neonatologists can provide care and work with other specialists to manage the condition.
• Hematologists: In some cases, patients with Crigler-Najjar syndrome may need regular, sometimes lifelong, blood transfusions or other treatments to manage their symptoms, and hematologists can provide this care.
• Neurologists: In rare cases, high levels of bilirubin can damage the brain and nervous system, leading to brain damage or neurological problems, so it's important to see a neurologist if any symptoms of this occur.
• Endocrinologists: Some studies have shown that people with Crigler-Najjar syndrome may be at an increased risk of developing endocrine disorders, such as hypothyroidism, so it may be necessary to see an endocrinologist for this.
• Ophthalmologists: This disease may lead to yellowing of the eyes, so an ophthalmologist may be consulted to monitor for any complications.

These drugs are considered to be best for the treatment of Crigler-Najjar syndrome:

• Phenobarbital: A barbiturate drug that increases the liver's ability to conjugate bilirubin. Examples include Luminal, Solfoton, and Donnatal.
• Ursodeoxycholic acid: A bile acid that increases the excretion of bilirubin in feces. Examples include Actigall and Urso.

The length of time it takes for someone with Crigler-Najjar syndrome to heal varies on how severe their disease is and how well they respond to therapy. The condition does not presently have a cure, although therapy may help control the symptoms and avoid consequences. The most popular form of treatment for the illness is phototherapy, which includes being exposed to blue light. A liver transplant may be required in extreme situations. With proper treatment, people with Crigler-Najjar syndrome can lead normal lives, but ongoing management is usually required.

Recovery from Crigler-Najjar syndrome depends on the treatment plan and remission achieved from the treatments. Medical therapies, in combination with dietary changes, can lead to long-term remission over several months or years. Most affected individuals require lifelong management of their condition to prevent remissions and acute complications.

Here are some post-treatment guidelines for individuals with Crigler-Najjar syndrome:

• Follow a strict phototherapy regimen: Phototherapy is the primary treatment for Crigler-Najjar syndrome. It is important to adhere to the recommended phototherapy schedule to maintain safe bilirubin levels.
• Monitor bilirubin levels: Regular monitoring of bilirubin levels is necessary to ensure that they remain within a safe range. This may require frequent blood tests.
• Avoid triggers: Certain triggers, such as fasting, dehydration, or illness, can increase bilirubin levels. It's crucial to keep away from these triggers whenever you can.
• Take medication as prescribed: Some medications, such as phenobarbital, can help reduce bilirubin levels. It's crucial to take these drugs exactly as your doctor has advised.
• Maintain a healthy lifestyle: The risk of problems may be decreased and general health can be improved with a balanced diet and frequent exercise.
• Stay informed: It is important to stay up-to-date on the latest research and developments in the treatment of Crigler-Najjar syndrome. Individuals may be better able to control their disease and make educated choices about their care as a result.
• Consider genetic counseling: Crigler-Najjar syndrome is a genetic disorder. Genetic counseling may help people with the illness and their families better understand the risks and effects of the condition.

Depending on the severity of the ailment and the facility of choice, the cost of treating Crigler-Najjar syndrome in India might vary. The typical cost of therapy, however, might be between Rs. 10 lakhs and Rs. 20 lakhs.

This covers costs for hospitalization, medical examinations, prescriptions, and expert consultations.

Additional expenses may also include liver transplantation, which can cost upwards of Rs. 25 lakhs. It is important to note that these are approximate costs and may vary significantly depending on the individual case and hospital chosen.

The major side-effects of Crigler-Najjar syndrome treatments:

• Phototherapy side effects: As one of the primary treatments for Crigler-Najjar syndrome, phototherapy involves exposing the patient to bright light to improve the breakdown of jaundice-causing bilirubin in the liver. However, the side effects of phototherapy for Crigler-Najjar syndrome may include dehydration, skin irritation, eye damage or cataracts, and overheating.
• Medication side effects: Another way to treat Crigler-Najjar syndrome involves the use of medications such as phenobarbital or ursodeoxycholic acid to increase the production of bilirubin-conjugating enzymes in the liver. Nevertheless, these drugs might also cause liver damage, constipation, migraines, and dizziness as adverse effects.
• Liver transplantation side effects: A liver transplant may be required in extreme instances of Crigler-Najjar syndrome to replace the diseased liver with a healthy one. However, this invasive procedure carries the risk of complications such as bleeding, infection, organ rejection or failure, and needing lifelong immunosuppressant medication.

.If you experience any complications associated with Crigler-Najjar syndrome, you should see a doctor in your area right away. These complications include 'Kernicterus, jaundice, liver failure, fatigue,' and the necessary treatment may take anywhere from a few months to years, depending on how severe the problem is.