Journal Information
Journal ID (publisher-id): BM
Journal ID (nlm-ta): Biochem Med (Zagreb)
Title: Biochemia Medica
Abbreviated Title: Biochem. Med. (Zagreb)
ISSN (print): 1330-0962
ISSN (electronic): 1846-7482
Publisher: Croatian Society of Medical Biochemistry and Laboratory Medicine
Article Information
Copyright statement: ©Croatian Society of Medical Biochemistry and Laboratory Medicine.
Copyright: 2023, Croatian Society of Medical Biochemistry
License (open-access):
This is an Open Access article distributed under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Date received: 15 April 2024
Date accepted: 20 August 2024
Publication date: 15 October 2024
Publication date: 15 October 2024
Volume: 34
Issue: 3
Electronic Location Identifier: 031002
Publisher ID: bm-34-3-031002
DOI: 10.11613/BM.2024.031002
A case of alkaptonuria presenting with unexplained dark-stained diapers and spurious hyperoxaluria and proteinuria due to homogentisic acid interference
Thibault Vanhove[1]
[1] Clinical Department of Laboratory Medicine, UZ Leuven, Leuven, Belgium
[2] Department of Paediatric Nephrology, UZ Leuven, Leuven, Belgium
[3] Department of Oncology, KU Leuven, Leuven, Belgium
[4] Centre for Metabolic Diseases, Department of Pediatrics, UZ Leuven, Leuven, Belgium
[5] Department of Development and Regeneration, KU Leuven, Leuven, Belgium
[6] Department of Cellular and Molecular Physiology, KU Leuven, Leuven, Belgium
[7] Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
[8] Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
Author notes:
Last two authors equally contributed as senior authors.
[*] Corresponding author: pieter.vermeersch@uzleuven.be
Author contributions
P Vermeersch, G Frans: Conceptualization, Writing – original draft, review & editing; T Vanhove: Writing – original draft, review & editing; M Aertgeerts, P Witters, D Rymen, D Böckenhauer: Writing – review & editing.
• Homogentisic acid (HGA) can cause a false increase of urinary results expressed per creatinine and a false increase of urine total protein measured with a method using benzethonium chloride
• Alkaptonuria should be excluded in patients with unexplained high urine total protein without concomitant albuminuria
• In patients with alkaptonuria urine creatinine should be measured using a method that is not susceptible to interference by HGA, such as LC-MS/MS
• Suspected samples can be tested by adding alkaline solution to urine or dried spots to detect dark discoloration
Alkaptonuria is characterized by the accumulation of homogentisic acid which causes dark coloration of urine upon standing, ochronosis, and arthritis. A 4-year old child was referred to our pediatric nephrologist with hyperoxaluria and a history of unexplained pink-to-brown discolouration of his diapers associated with a brown-staining of clothes and skin since he was six months old. He had no other symptoms and his past medical history only included minor child illnesses. His 11-month-old brother had the same dark discoloration of his diapers. Laboratory testing on a spot urine sample showed hyperoxaluria and nephrotic range proteinuria with low creatinine and normal albumin concentrations. Considered causes were hyperoxaluria, alkaptonuria, interfering substance, adulteration. The further diagnostic work-up revealed increased homogentisic acid in urine, compatible with alkaptonuria. Urinary creatinine and total protein measurements on Roche Cobas were, respectively, falsely decreased and increased in the presence of homogentisic acid. The false-low creatinine resulted in an elevated oxalate/creatinine ratio. Alkaptonuria can cause a false increase of results expressed per creatinine and should be excluded in case of an unexplained marked increase of urine total protein without a concomitant increase of albumin.
Keywords: preanalytical phase; interference; homogentisic acid; dark-stained urine; alkaptonuria; inborn errors of metabolism; case report
