Abstract
Based on the clinical course of a 16-year-old boy with type I Crigler-Najjar syndrome, we estimated the threshold concentration of unbound bilirubin, as assayed by the horseradish peroxidase method, that apparently induces toxicity to the brain. Before the age of 15, the patient did not manifest any neurological or behavioural dysfunction despite increased bilirubin in serum. The binding affinity and the binding capacity of the patient's serum albumin for bilirubin determined when he was about 14 years old were 108(mol/L)−1 and 1·01 to 1·04 mol/L, respectively. These values were nearly the same as those of normal controls reported in the literature. The total bilirubin binding capacity was greater than the patient's total bilirubin concentration, showing that his serum albumin was not saturated with bilirubin. The reserve bilirubin binding capacity (RBBC) was estimated to be 158 μmol/L and the unbound bilirubin concentration to be 15·1 nmol/L. Concentration of unbound bilirubin peaked at 21·7 nmol/L at the age of 15 years and 11 months, i.e. 2 months before the onset of difficulties in walking and speaking. At this time, the RBBC was estimated as −64 μmol/L. A peak concentration of total bilirubin, 811 μmol/L, was observed during the period of rapid loss of the ability to walk or speak. At the age of 16 years and 1 month the RBBC decreased to −98 μmol/L and the unbound bilirubin concentration to 18·8 nmol/L. Following phototherapy, the patient's neurological state returned to normal; he could speak and walk normally. At the age of 16 years and 2 months the RBBC returned to 105 μmol/L and unbound bilirubin decreased to 16·6 nmol/L. These results suggest that maintaining the concentration of unbound bilirubin at < 20 nmol/L and the total bilirubin concentration at lower than the binding capacity of serum albumin is important for prevention of neurological deficits in Crigler-Najjar syndrome. The upper limit of unbound bilirubin in such an older patient was nearly the same as that reported for newborns.