Screening of patients with Crigler-Najjar

Crigler-Najjar syndrome is arare, recessive inherited disorder caused by
deficiency of uridine diphosphoglucuronosyl transferase (UGT1A1). UGT1A1 is an
enzyme which catalyzes the glucuronidation of unconjugated bilirubin, an
essential step in the excretion into bile of this neurotoxic compound. Patients
with Crigler-Najjar suffer from severe unconjugated hyperbilirubinemia and are
at risk of bilirubin encephalopathy. The standard treatment for Crigler-Najjar
is phototherapy during early childhood and when later in life serum bilirubin
levels start to increase above 400µmol/L a liver transplantation is performed.
The extensive phototherapy and the side effects of life-long immune suppression
warrant the development of liver directed gene therapy. Crigler-Najjar syndrome
seems to be an attractive disorder for the development of liver directed gene
therapy, because no liver damage is present. Before a phase l/ll clinical trial
with gene therapy in the treatment of Crigler-Najjar is started, a careful
screening of patients with Crigler-Najjar syndrome should be performed to
determine which patients could be taken in consideration to participate in the
up coming clinical trial. The screen will consist of serology on the presence
of Hepatitis B and C and AAV8 antibodies, fibroscan, ultrasound of the abdomen
and serum livertests.

Screening of patients with the inherited liver disease Crigler-Najjar.

A visit to the outpatient clinic bloodsamples, questionaires, ultrasound and
fibroscan will be performed.

The burden consists of only one visit to the hospital and one venapunction. The
risk for the patients is very low.