IllnessCrigler-Najjar syndrome type II, unconjugated hyperbilirubinemia

NGS + X

Sanger

Crigler-Najjar syndrome is a severe disorder characterized by critical hyperbilirubinemia (unconjugated). Jaundice occurs at birth or in infancy, possibly with kernicterus. Infants are then lethargic and hypotensive, possibly with episodes of hypertension and extensor spasms. Kernicterus may lead to choreoathetosis, hearing problems and/or mental retardation. Crigler-Najjar syndrome is divided into two types. Type 1 is very severe, and affected individuals may die of kernicterus in childhood, although appropriate therapy may prolong survival. Type 2 is less severe, kernicterus is less common, and most affected individuals survive into adulthood. Approximately 1 in 1 million newborns worldwide are affected by Crigler-Najjar syndromes types 1 and 2. Mutations in the UGT1A1 gene cause this disease with absent or severely reduced function of the bilirubin UGT enzyme, resulting in reduced glucuronidation of unconjugated bilirubin. Affected individuals with type 1 have no enzyme function, whereas type 2 exhibits <20% of normal enzymatic activity. Crigler-Najjar syndrome is inherited in an autosomal recessive manner. The symptoms of type II may resemble severe forms of Gilbert syndrome (Meulengracht disease). The quality of clinical characterization largely determines the yield of the molecular genetic diagnostics. A negative DNA test result does not exclude the clinical diagnosis with certainty.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK114805/

Laboratory data:

Crigler-Najjar syndrome type 1: total serum bilirubin 20-45mg/dL [complete UGT1A1 deficiency].

Crigler-Najjar syndrome type 2: total serum bilirubin 6-20mg/dL [<20% UGT1A1 activity].

DD: Gilbert syndrome/M. Meulengracht: total serum bilirubin 1-6mg/dL [UGT1A1 promoter deficiency].

• Def.: Crigler-Najjar syndrome type I: total serum bilirubin 20-45mg/dL [complete UGT1A1 deficiency]
• Def.: Crigler-Najjar syndrome type II: total serum bilirubin 6-20mg/dL [partial UGT1A1 deficiency]
• Def.: Meulengracht/Gilbert syndrome: total serum bilirubin 1-6mg/dL [UGT1A1 promotor deficiency]
• Alias: Bilirubin uridinediphosphate glucuronosyltransferase deficiency type 2 (UGT1A1)
• Alias: Bilirubin-UGT deficiency type 2 (UGT1A1)
• Alias: Familial nonhemolytic unconjugated hyperbilirubinemia (UGT1A1)
• Alias: Hereditary unconjugated hyperbilirubinemia type 2 (UGT1A1)
• Alias: Hyperbilirubinemia, Crigler-Najjar type II (UGT1A1)
• Alias: UGT deficiency type 2 (UGT1A1)
• Allelic: Arias syndrome (UGT1A1)
• Allelic: Crigler-Najjar syndrome, type I (UGT1A1)
• Allelic: Gilbert [Gilbert-Meulengracht] syndrome (UGT1A1)
• Crigler-Najjar syndrome, type II (UGT1A1)