Standard values for the urine HVA/VMA ratio in neonates as a screen for Menkes disease

Abstract Background: Menkes disease is a lethal disorder associated with copper metabolism. Although early treatment with copper-histidine injections can improve outcomes, early diagnosis is difficult because the clinical features of Menkes disease are subtle or do not manifest in affected neonates. Previous report stated that the low activity of dopamine β-hydroxylase, a copper-dependent enzyme, leads to increases in the urine homovanillic acid/vanillylmandelic acid (HVA/VMA) ratios in patients with Menkes disease, and indicated that a urine HVA/VMA ratio cut-off value of >4 is useful in screening for Menkes disease. Methods : We examined the standard values of the urine HVA/VMA ratio in unaffected neonates and assessed its use as a screening parameter for Menkes disease among neonates. In total, 112 neonates, aged between 1 and 6 days, were enrolled in the study and were classified into 2 groups based on their urine HVA/VMA ratios: high (>4) and low (⩽4). Results : Multivariate logistic analysis revealed that mechanical ventilation was an independent risk factor for a high urine HVA/VMA ratio (odds ratio: 21.94; 95% confidence interval: 2.82–247.03; p  = 0.004). The mean urine HVA/VMA ratio was 2.47 ± 0.67 among 92 neonates who did not receive mechanical ventilation. Conclusion : This study established standard values for the urine HVA/VMA ratio in newborn babies that could be useful in screening for Menkes disease among neonates.