Endocrine Abstracts

JOINT148

Background: The ultra -old problem of neonatal hyperbilirubinemia has been solved by complex settings of exchange transfusion and phototherapy and beside time/cost and ward consuming issues; treatment is not optimum. Till now it has not been clarified whether low grade hyperbilirubinemia is harmful or beneficial regarding the antioxidant nature of unconjugated bilirubin. Besides Albumin binding, transportation to the liver, uptake, conjugation and secretion into bile has not been fully investigated for therapeutic intervention. Conjugation within the circulation omits these steps and will be faster than natural absorption, conjugation and release. We proposed that peripheral conjugation with a canine glucose transferase short cut all these steps without the need for the energy rich uridyl-glucuronic-transferase which is relatively deficient in neonates in premature babies.

Methods: After successful preclinical study, two enzymes i. e. human glucuronic transferase and canine glucose transferase were used at in 12 patients in three clinical phases. Type I Crigler Najjar models were not available so moribund neonates with life expectancy of less than three months were used for toxicity studies.

Results: The human enzyme was unable to conjugate bilirubin in human serum because of the lack of uridyl-diphosphate. Addition of uridyl-diphosphate completed the task within minutes. Conjugation with glucose under canine glucose transferase was easy, without the need for uridyl-diphosphate and resulted in water soluble monoconjugates. The reaction was completed within seconds without complex needed agents or by products In vitro. In vitro studies of hundreds of blood samples were extremely successful with glucose transferase. The details are out of the scope of this presentation. A single injection caused a reduction of harmless Bilirubin of 8mg/dl down to zero in a timely curve in 12 human neonates.

Conclusion: Treatment of neonatal hyperbilirubinemia with canine glucose transferase at picogram concentrations is safe and can be accomplished as treatment and prophylaxis.