Interference of hydroxyphenylpyruvic acid, hydroxyphenyllactic acid and tyrosine on routine serum and urine clinical chemistry assays; implications for biochemical monitoring of patients with alkaptonuria treated with nitisinone.

Abstract

OBJECTIVES:

We have assessed the effect of elevated concentrations of hydroxyphenylpyruvic acid (HPPA), hydroxyphenyllactic acid (HPLA) and tyrosine, on a range of chemistry tests in serum and urine to explore the potential for chemical interference on routine laboratory analyses in patients with alkaptonuria (AKU) treated with nitisinone and similarly implications for patients with hereditary tyrosinemia type 1 (HT-1).

MATERIALS AND METHODS:

HPPA, HPLA and tyrosine were added separately to pooled serum from subjects without AKU in a range of assays with Roche Modular chemistries. Effects on urine were assessed by changes in urine strip chemistries after mixing a positive control urine with various amounts of the test compounds and reading on a Siemens urine strip meter.

RESULTS:

No significant effect (p > 0.1) was observed up to 225 μmol/L of HPPA and HPLA, and up to 5000 μmol/L tyrosine, on any of the serum-based assays including those with peroxidase-coupled reaction systems of enzymatic creatinine, urate, total cholesterol, HDL cholesterol and triglyceride. Both the monohydroxy HPPA, and the dihydroxy homogentisic acid (HGA), at increased urine concentrations typical of nitisinone-treated AKU and non-treated AKU respectively, did however show marked negative interference in strip assays for glucose and leucocytes; i.e. those with peroxide-linked endpoints. The effect of increased HPLA was less marked.

CONCLUSIONS:

In patients with AKU or on nitisinone treatment and HT-1 patients on nitisinone, urine strip chemistry testing should be used sparingly, if at all, to avoid false negative reporting. It is recommended that urine assays should be organised with a suitable specialist laboratory.

• Authors: S L Curtis, B P Norman, A M Milan, J A Gallagher, B Olsson, L R Ranganath, N B Roberts
• Journal: Clinical biochemistry (Clin Biochem) Vol. 71 Pg. 24-30 (Sep 2019) ISSN: 1873-2933 [Electronic] United States
• PMID: 31228435 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cyclohexanones
• Enzyme Inhibitors
• Nitrobenzoates
• Phenylpropionates
• Phenylpyruvic Acids
• 4-hydroxyphenylpyruvic acid
• 4-hydroxyphenyllactic acid
• Tyrosine
• 4-Hydroxyphenylpyruvate Dioxygenase
• nitisinone

Topics

• 4-Hydroxyphenylpyruvate Dioxygenase (metabolism)
• Alkaptonuria (blood, drug therapy, metabolism, urine)
• Cyclohexanones (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Humans
• Nitrobenzoates (therapeutic use)
• Phenylpropionates (analysis, blood, urine)
• Phenylpyruvic Acids (analysis, blood, urine)
• Tyrosine (metabolism)