Urinary excretion of HMMA and HVA in infants

Area of Science:

• Biochemistry
• Pediatric Oncology
• Analytical Chemistry

Background:

• Accurate reference ranges for urinary homovanillic acid (HVA) and 4-hydroxy-3-methoxymandelic acid (VMA) are essential for neuroblastoma screening in infants.
• Previous studies may lack comprehensive data for large infant cohorts.

Purpose of the Study:

• To establish normal urinary excretion values for HVA and VMA in a large cohort of 6-month-old infants.
• To provide essential reference data for the development of population-based neuroblastoma screening programs.
• To investigate potential causes of apparent elevated metabolite levels in infant urine samples.

Main Methods:

• Gas chromatography with flame ionization detection (GC-FID) was employed to quantify HVA and VMA.
• Urinary samples from 808 infants aged 6 months were analyzed.
• Gas chromatography/mass spectrometry (GC/MS) was used to validate results for samples with apparent increased metabolite excretion.

Main Results:

• Mean urinary HVA excretion was 10.9 mumol/mmol creatinine, with an upper 95% confidence interval of 25.5 mumol/mmol creatinine.
• Mean urinary VMA excretion was 6.8 mumol/mmol creatinine, with an upper 95% confidence interval of 15.0 mumol/mmol creatinine.
• GC/MS analysis of 39 samples (4.8%) with apparent increased excretion confirmed that interfering chromatographic peaks, not true elevation, were the cause.

Conclusions:

• The established reference ranges for urinary HVA and VMA provide a critical baseline for infant neuroblastoma screening.
• The study demonstrates the reliability of GC-FID for routine screening, with GC/MS serving as a valuable tool for resolving analytical interferences.
• These findings support the feasibility of population-based screening for neuroblastoma in infants using urinary catecholamine metabolite analysis.