Crigler-Najjar syndrome ... (Crigler-Najjar syndrome) - Gen UGT1A1.
Crigler-Najjar is a serious hereditary disorder characterized by high blood levels of bilirubin (hyperbilirubinemia) and jaundice. Bilirubin is eliminated from the body only after unconjugated bilirubin becomes conjugated bilirubin. In Crigler-Najjar syndrome, jaundice is apparent at birth or childhood. Severe hyperbilirubinemia can lead to kernicterus, which can cause serious damage to the central nervous system, such as bilirubin encephalopathy (kernicterus), usually fatal, or may leave permanent neurological sequelae. Newborns with kernicterus can manifest lethargy, hypotonia, hypertonia and arched. In addition, kernicterus can cause other neurological problems, including coreoatetosis, hearing problems or intellectual disabilities.
The Crigler-Najjar syndrome is divided into two types: type 1 (CN1) is very serious, and affected individuals may die in infancy because of kernicterus, but with proper treatment, can survive longer; Type 2 (CN2) is less severe and those affected are less likely to develop kernicterus, and most affected individuals survive to adulthood.
This process is due to mutations in the UGT1A1 gene, located on the long arm of chromosome 2 (2q37). The gene encoding UGT1A1 enzyme bilirubin uridinadifosfato glucuronosyltransferase (UGT bilirubin), found mainly in hepatocytes cells and is necessary for the removal of bilirubin in the body. Bilirubin-UGT enzyme performs the chemical reaction of glucuronidation. During this reaction, the enzyme converts unconjugated bilirubin in unconjugated bilirubin. Conjugated bilirubin dissolves in bile and excreted with solid waste.
They have identified at least 85 mutations in the UGT1A1 gene in people with Crigler-Najjar syndrome. Genetic lesions of individuals with Crigler-Najjar syndrome, both type I and type II, can take place in any of the five exons that comprise the UGT1A1 gene. Mutations that involve the removal or alteration of a large number of amino acids, typically change the reading frame or premature stop codon, usually cause enzyme inactivation bilirubin-UGT and therefore be associated with CN1 while persons with Crigler-Najjar type 2 (CN2) syndrome have less than 20% of the normal function of the bilirubin-UGT. However, there have also been localized point mutations, usually associated with CN2, causing the complete enzyme inactivation (CN1) to be located at highly conserved regions or essential regions.
Crigler-Najjar is inherited in an autosomal recessive pattern, which means that both copies of the UGT1A1 gene in each cell have mutations. A less severe condition called Gilbert syndrome may occur when a copy of the UGT1A1 gene has a mutation.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Crigler-Najjar syndrome, by complete PCR amplification of the exons of the UGT1A1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated card with dried blood sample if postnatal diagnosis. (IVAMI can mail the card to deposit the blood sample).