SNP Shot: Genomic Insights

Crigler-Najjar syndrome is a serious disorder marked by elevated bilirubin levels in the blood, a condition known as hyperbilirubinemia. Bilirubin, a toxic compound, is a byproduct of red blood cell breakdown. Normally, the liver detoxifies bilirubin by converting it from an unconjugated (toxic) form to a conjugated (non-toxic) form, enabling its removal from the body. Individuals with Crigler-Najjar syndrome experience a buildup of unconjugated bilirubin, resulting in unconjugated hyperbilirubinemia.

Bilirubin's orange-yellow color causes jaundice, a yellowing of the skin and eyes, when hyperbilirubinemia is present. In Crigler-Najjar syndrome, jaundice is noticeable from birth or early infancy. Severe unconjugated hyperbilirubinemia can lead to kernicterus, a dangerous form of brain damage. Kernicterus results from the accumulation of unconjugated bilirubin in the brain and nerve tissues. Infants with kernicterus often display extreme lethargy and reduced muscle tone (hypotonia). They may also exhibit periods of increased muscle tone (hypertonia) and back arching. Kernicterus can cause various neurological issues, including involuntary, writhing movements (choreoathetosis), hearing impairment, and intellectual disability.

Crigler-Najjar syndrome is classified into two types: Type 1 (CN1) and Type 2 (CN2). CN1 is the more severe form, and without adequate treatment, individuals with CN1 may die in childhood due to kernicterus. With appropriate management, survival can be extended. CN2 is less severe; kernicterus is less likely to develop, and most individuals with CN2 live into adulthood.

Inheritance:

Crigler-Najjar syndrome follows an autosomal recessive inheritance pattern. This means that both copies of the UGT1A1 gene in each cell must carry a mutation for the condition to manifest. Gilbert syndrome, a milder condition, can develop if only one copy of the UGT1A1 gene is mutated.