Homovanillic acid and vanillylmandelic acid as neuroblastoma biomarkers in children

Neuroblastoma (NBL) is the most common pediatric tumor with the highest fatality rate.The survival rate is improved when NBL is diagnosed in children under 1 year of age, but the diagnosis is complex due to the heterogeneity of the disease.This tumor type is characterized by elevated catecholamines and their metabolites, particularly homovanillic acid (HVA) and vanillylmandelic acid (VMA).Numerous analytical methods measuring urinary HVA and VMA have been developed to support the early NBL diagnosis.However, it is difficult to establish age-related reference ranges for these tests in children.To support the diagnostic process, the aim of this review is to provide up-to-date published age-related HVA and VMA reference intervals with focus on neuroblastoma development, catecholamine metabolism and possible interferences in the analytical methods used.