Low or undetectable alkaline phosphatase activity is a relatively uncommon finding. Artifactual decreases in alkaline phosphatase activity can occur in the absence of divalent cations needed as cofactors. In a review of almost 70 000 alkaline phosphatase results for adult, mainly male, patients, Lum found low activity in only 0.19% (1). In half of the cases reviewed, there was no explainable cause for the low results. The most common explainable cause was cardiac surgery, and malnutrition and magnesium deficiency were the next most common causes. All of these causes can be associated with either low levels of cations such as magnesium and zinc or the presence of chelators, such as citrate, in transfusions that lower alkaline phosphatase activity. Contamination of “serum” by EDTA or citrate during phlebotomy can cause undetectable alkaline phosphatase activity. Clinically apparent causes of low alkaline phosphatase include the rare congenital disorder hypophosphatasia, use of estrogens (including estrogen-containing oral contraceptives), and severe hypothyroidism. As seen in the current case, low alkaline phosphatase activity is also seen in fulminant hepatitis due to Wilson disease. Because none of the other causes of low alkaline phosphatase activity would be associated with jaundice or hemolytic anemia, the combination of these findings should lead the astute laboratorian to contact the clinicians to make sure that they consider Wilson disease as a diagnostic possibility. As described well here, tests more commonly used for Wilson disease diagnosis are often unreliable in the setting of acute liver failure. In a review of cases of acute liver failure in children, 54% of those with “unexplained” causes had never been evaluated for Wilson disease (2). Laboratory professionals should be alert to this uncommon cause of a rare laboratory finding, which can be lifesaving if the correct diagnosis of Wilson disease is made.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: D.R. Dufour, Clinical Chemistry, AACC.
Consultant or Advisory Role: D.R. Dufour, Ortho Clinical Diagnostics.
Stock Ownership: None declared.
Honoraria: D.R. Dufour, Osler Institute and College of American Pathologists.
Research Funding: None declared.
Expert Testimony: None declared.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication October 21, 2010.
- Accepted for publication October 28, 2010.
- © 2010 The American Association for Clinical Chemistry