ACETAMINOPHEN TOXICITY IN CHILDREN - DIAGNOSTIC CONFIRMATION USING A SPECIFIC ANTIGENIC BIOMARKER

Chronic acetaminophen (APAP) toxicity poses a difficult diagnostic cha llenge to the clinician. Signs and symptoms are nonspecific and no cur rently available laboratory study can confirm APAP as the causative ag ent of hepatic injury. In this study an antigenic biomarker for APAP t oxicity was used to confirm the diagnosis of APAP-induced hepatic fail ure in two children with chronic APAP toxicity. APAP that has been met abolized to N-acetyl-benzoquinone imine (NAPQI) reacts with cellular p roteins to form 3-(cystein-S-yl)-APAP protein adducts (3-Cys-A). Serum from both patients was submitted for quantitation of 3-Cys-A by a com petitive inhibition enzyme-linked immunosorbent assay (ELISA). Concent rations of 3-Cys-A in the two patients were 1.97 and 2.77 nmol/mg prot ein, which are similar to concentrations found in adults with hepatic injury secondary to an overdose of APAP. Individuals with no exposure to APAP have no detectable 3-Cys-A in serum. It was concluded that 3-C ys-A is a useful marker of APAP intoxication after long-term ingestion of APAP when total dose and time course of ingestion are uncertain, a nd may prove to be a useful clinical and investigative tool in the stu dy of APAP intoxication.