Crigler-Najjar Syndrome
Description
Crigler-Najjar Syndrome (CNS) is a rare, inherited metabolic disorder characterized by the inability to properly process bilirubin, a yellow pigment produced during the breakdown of heme, a component of red blood cells. This leads to a buildup of bilirubin in the blood, causing jaundice (yellowing of the skin and eyes). CNS is typically diagnosed in newborns and can range in severity, with some individuals experiencing mild symptoms while others require significant medical intervention.
Genes Involved
Genes Involved in Crigler-Najjar Syndrome:
- UGT1A1: The primary gene associated with CNS is UGT1A1, which provides instructions for producing the enzyme uridine 5‘-diphospho-glucuronosyltransferase 1A1 (UGT1A1). This enzyme is crucial for conjugating bilirubin, making it water-soluble and allowing it to be excreted in bile. Mutations in the UGT1A1 gene disrupt this process, leading to bilirubin buildup.
Recognizing the Signs and Symptoms
Recognizing the Signs and Symptoms of Crigler-Najjar Syndrome:
- Jaundice: The most prominent symptom of CNS is persistent, intense jaundice, which is often present at birth or shortly after.
- Kernicterus: In severe cases, high levels of bilirubin can damage the brain, leading to kernicterus, which can cause developmental delays, cerebral palsy, hearing loss, and other neurological complications.
- Dark urine: Bilirubin can be excreted in the urine, leading to a dark, tea-colored appearance.
- Pale stools: Due to reduced bilirubin excretion in the bile, stools may appear pale or clay-colored.
- Enlarged liver and spleen: In some cases, the liver and spleen may become enlarged.
Causes
Causes of Crigler-Najjar Syndrome:
- Genetic inheritance: CNS is an autosomal recessive disorder, meaning that both parents must carry the mutated gene for their child to inherit the condition. If both parents are carriers, there is a 25% chance that each child will inherit the condition.
Inheritance/recurrence risk
Inheritance and Recurrence Risk of Crigler-Najjar Syndrome:
- Autosomal recessive: CNS is inherited in an autosomal recessive manner. This means that both parents must carry a copy of the mutated gene for their child to inherit the condition. Each child of two carrier parents has a 25% chance of inheriting the disorder, a 50% chance of being a carrier, and a 25% chance of inheriting two normal copies of the gene.
- Recurrence risk: If two parents have a child with CNS, there is a 25% chance that each subsequent child will also inherit the condition.
