title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Pediatrics, Nikoniko House Medical and Welfare Center, Kobe, Japan. Electronic address: marikoyagi.sgt@gmail.com.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kusunoki
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Nagasaka
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Koda
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miwa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Morioka
authors.affiliation: Department of Health and Dietetics, Teikyo Heisei University, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kodama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D002851:Chromatography, High Pressure Liquid; D042241:Early Diagnosis; D005260:Female; D006719:Homovanillic Acid / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000175:diagnosis* / Q000652:urine*; D012016:Reference Values; D014642:Vanilmandelic Acid / Q000652:urine*
chemical_list: D014642:Vanilmandelic Acid; D006719:Homovanillic Acid
keywords: Dopamine β-hydroxylase; Homovanillic acid/vanillylmandelic acid ratio; Menkes disease; Neonatal screening; Urine