Crigler-Najjar Syndrome: An Unusual Course with Development of Neurologic Damage at Age Eighteen

Abstract

A patient with t_ype I congenital nonhemolytic jaundice (type I Crigler-Najjar syndrome (CNJ)), who first developed overt neurologic sig& at age 18, is reported.Studies with isotopic bilirubin, performed both when she was well and after the onset of brain damage, demonstrated normal hepatic bilirubin uptake and storage capacity, and normal bilirubin turnover (3.0 mg/kg/24 hr). As a result of a virtual absence of conjugation, net bilirubin clearance was reduced to 0.0075 ml/min/kg, which is approximately 1 % of normal (0.G5 =t 0.18 ml/min/kg) . Therapy with glutethimide, phenobarbital, blue light, and oral agar were all ineffective in reducing the concentration of unconjugated bilirubin in plasma or accelerating radiobilirubin disappearance.The acute onset of neurologic disease occurred at age 18, and may possibly have related to a transient increase in the molar bilirubin to albumin ratio to a value greater than 1.0. Exchange plasmapheresis, performed with a continuous flow centrifuge, rapidly reduced the bilirubin concentration in plasma from 41 to 6 mg/100 ml, and was associated with apparent clinical improvement. A total of 1,900 mg bilirubin was removed by this procedure.Although in vivo phototherapy was ineffective, in vitro illumination of the patient's plasma with special blue lamps produced a rapid fall in the bilirubin concentration in plasma. Bilirubin was converted to polar, diazo-negative derivatives by a process in which several steps could be distinguished. The initial photodegradation products were colored, tightly albumin bound and nondialyzable, which explained their tendency to be excreted in the bile in preference to the urine. Continued illumination for up to 24 hr resulted in the production of colorless, nonalbumin-bound compounds which, when injected into rats, were excreted principally in the urine.

Unconjugated Bilirubin and an Increased Proportion of Bilirubin Monoconjugates in the Bile of Patients with Gilbert's Syndrome and Crigler-Najjar Disease

“…Crigler-Najjar disease, in agreement with other work (22,49,50). This, however, does not offer an absolute diagnostic criterion, as values approaching zero were occasionally found in patients with Gilbert's syndrome (50,51) and in neonates without liver disease (52).…”

“…A situation of this sort seems to exist in Gunn rats whose liver has a normal amounit of UDP-GTA actinig on p-nitrophenol with an abnormally low affinity for UDP-glucuronic acid (57). The near-zero tranisferase activities typically found in the liver of CriglerNajjar patients (Table 1) (22,49,50) are consistent with the low biliary output of bilirubin con-jugates in this condition (54,55 …”

Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

“…The mean value for BSP K1 in the patients with Gilbert's syndrome was 0-133 ± 0-032 which did not differ significantly from the normal value of 0-145 ± 0-017 (Fauvert, 1959) or 0-14 ± 0-02 less than 5 % (Combes and Schenker, 1969;Blaschke et al, 1974).…”

Hepatic organic anion uptake in the rat.

“…The actual BR concentration in this solution was then measured in duplicate before its use for bolus injections or infusion. BR photodegradation products were formed in vitro by a method similar to that previously described (7). A concentrated (240 mg/ 100 ml) solution of BR in rat plasma was circulated around Westinghouse Special Blue bulbs (F20T12/BB) (Westinghouse Electric Corp., Pittsburgh, Pa.) for 16 h.…”