Crigler-Najjar syndrome (CNS) is an extremely rare genetic condition caused by the total or partial lack of an enzyme that breaks down the waste product bilirubin in the liver. Bilirubin is created when the body breaks down old red blood cells. There are two types of CNS. CNS type 1 (CNS1) is the more severe condition, resulting in extremely high levels of bilirubin in the blood, which if left untreated may result in deafness, brain damage and death. CNS1 can be controlled by regular treatment with intense beams of light (phototherapy) to break down the bilirubin, but the patient will eventually require a liver transplant. CNS type 2 (CNS2) is associated with lower levels of bilirubin and is therefore less severe; it can be treated with phenobarbital. In this study, we wish to use data from general practice and hospital sources within CPRD to study patients with CNS and to describe them in terms of their age at diagnosis, gender, the effects of their disease, how it is monitored and treated, and rates of liver transplant and death.
We aim to define a cohort of patients with Crigler-Najjar syndrome (CNS) and create patient profiles of relevant characteristics to determine, firstly, CNS type (CNS1 or CNS2) and, secondly, to follow the natural history of the condition. Data will be selected from CPRD, including linked HES inpatient and outpatient data and ONS mortality data. Patient profiles will be constructed for patients with relevant Read or ICD-10 codes including demographics, age at diagnosis, treatment pathways, longitudinal change in bilirubin values, rates of inpatient, outpatient and primary care contacts, and mortality and liver transplant rates.
Health Outcomes to be Measured:
a) Gender, age, location (based on the UK nation or English strategic health authority region in which the patient's primary care practice is located) b) CNS type. There are no classification codes to distinguish between CNS1 and CNS2, therefore we will use the decision rules outlined in Table 1. c) Age at first presentation d) Changes in diagnosis, that is the recording of other similar conditions such as Gilbert's disease e) Investigative procedures (liver biopsy, genotyping) f) Biochemistry - Serum bilirubin g) Family history based on siblings/parents with CNS sharing CPRD family number (patient histories will be compared to reduce the risk that patients are linked by shared accommodation only) h) Age when CNS treatment initiated by transfusion, phototherapy, phenobarbital i) Frequency of inpatient, outpatient and primary care contacts j) All therapeutics used for treatment or management purposes, and reasons for the therapies (based on ICD-10 or Read code) (from CPRD database only) k) Age at liver transplant l) Age at death; cause of death.
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation