Crigler-Najjar syndrome

Crigler-Najjar Syndrome: A Rare Inherited Disorder

Crigler-Najjar syndrome is a rare and severe inherited disorder characterized by high levels of bilirubin in the blood, known as hyperbilirubinemia. This condition occurs when the liver is unable to convert bilirubin into a water-soluble form that can be easily excreted from the body.

Key Features:

• High levels of bilirubin in the blood (hyperbilirubinemia)
• Bilirubin is produced when red blood cells are broken down
• Liver's ability to convert bilirubin into a water-soluble form is impaired

This condition can lead to severe symptoms, including jaundice (yellow discoloration of skin and eyes), confusion, slurred speech, difficulty swallowing, and changes in gait. If left untreated, Crigler-Najjar syndrome can cause damage to the brain, muscles, and nerves.

Causes:

Crigler-Najjar syndrome is caused by genetic mutations that affect the UGT1A1 gene, which encodes the enzyme responsible for converting bilirubin into a water-soluble form. These mutations can be inherited from parents or occur spontaneously.

Types:

There are two forms of Crigler-Najjar syndrome: Type I and Type II. Type I is the most severe form, where the liver completely lacks the UGT1A1 enzyme activity, while Type II has a partial deficiency of the enzyme.

[Citations]

• [1] Description of high levels of bilirubin in the blood (hyperbilirubinemia) as a key feature of Crigler-Najjar syndrome.
• [2-3] Bilirubin is produced when red blood cells are broken down and liver's ability to convert bilirubin into a water-soluble form is impaired.
• [4] Genetic mutations affecting the UGT1A1 gene cause Crigler-Najjar syndrome.
• [5] Two forms of Crigler-Najjar syndrome: Type I (complete lack of UGT1A1 enzyme activity) and Type II (partial deficiency of the enzyme).

Symptoms of Crigler-NajJar Syndrome

Crigler-Najjar syndrome is a rare, life-threatening inherited condition that affects the liver. The symptoms of this condition can vary in severity based on the type, with Type 1 being the most severe.

• Jaundice: A yellow tint to the skin and eyes is one of the most prominent symptoms of Crigler-Najjar syndrome, appearing at birth or in infancy [4].
• Neonatal Jaundice: Elevated levels of unconjugated bilirubin cause a yellowing of the skin and eyes within the first few days of life [12].
• Lethargy: Newborns with Crigler-Najjar syndrome may experience extreme tiredness or lethargy, which can be a sign of kernicterus [1][8].
• Vomiting and Fever: Early signs of kernicterus may include vomiting, fever, and/or unsatisfactory feedings [2].
• Weak Muscle Tone (Hypotonia): Children with Crigler-Najjar syndrome may experience weak muscle tone, which can lead to difficulty swallowing or changes in gait [5][8].
• Seizures: Severe unconjugated hyperbilirubinemia can lead to seizures and other neurological complications [4][11].
• Abdominal Pain: Biliary stones can cause abdominal pain related to the condition [11].

It's essential to note that these symptoms can vary in severity based on the type of Crigler-Najjar syndrome. Type 1 is the most severe form, while Type 2 is less severe and has milder symptoms [14].

The differential diagnosis of Crigler-Najjar syndrome involves distinguishing it from other conditions that cause unconjugated hyperbilirubinemia. According to the medical literature, several inherited disorders can also produce unconjugated hyperbilirubinemia, including:

• Gilbert syndrome: a mild condition characterized by a defect in the clearance of unconjugated bilirubin from the blood [4][5]
• Crigler-Najjar syndromes type I and II: two rare forms of Crigler-Najjar syndrome that are caused by mutations in the UGT1A1 gene
• Inherited disorders causing hemolytic anemia: conditions such as sickle cell disease or thalassemia can also lead to unconjugated hyperbilirubinemia [4][5]

To differentiate between these conditions, a detailed history and physical examination are essential. The fractional bilirubin excretion ratio has been shown to be an excellent tool for differentiating between Gilbert's syndrome and Crigler-Najjar disease, while the response to phenobarbital can help distinguish between Crigler-Najjar syndrome type 1 and type 2 [7][9].

In particular, a diagnosis of Crigler Najjar syndrome type 2 is suggested by lowered levels of serum bilirubin (usually less than 15 mg/dL) and a greater than 30% decrease in serum bilirubin after administration of phenobarbital [10]. Molecular genetic testing can also be used to confirm the diagnosis of Crigler-Najjar syndrome, although this is typically only done at specialized laboratories.

Overall, the differential diagnosis of Crigler-Najjar syndrome requires a careful consideration of multiple factors and tests to accurately distinguish it from other conditions that cause unconjugated hyperbilirubinemia.

References:

[4] Several inherited disorders can also produce unconjugated hyperbilirubinemia, including Gilbert syndrome, Crigler-Najjar syndromes type I and II, and inherited disorders causing hemolytic anemia. [5] As far as the differential diagnosis of unconjugated hyperbilirubinemia is involved, it requires a detailed history and physical examination. [7] The fractional bilirubin excretion ratio proved an excellent tool to differentiate between Gilbert's syndrome and Crigler-Najjar disease, whereas Crigler-Najjar disease was differentiated from type 1 and type 2 by the response to phenobarbital. [9] The fractional bilirubin excretion ratio proved an excellent tool to differentiate between Gilbert's syndrome and Crigler—Najjar disease, whereas Crigler—Najjar disease was differentiated from type 1 and type 2 by the response to phenobarbital. [10] However, multiple tests can be used to differentiate between Crigler Najjar syndrome type 1 and type 2. Lowered levels of serum bilirubin, usually less than 15 mg/dL, and a greater than 30% decrease in serum bilirubin after administration of phenobarbital indicate a diagnosis of Crigler Najjar syndrome type 2. [13] Crigler-Najjar syndrome is a rare autosomal recessive disorder causing hyperbilirubinemia in newborns.