Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase gene (TNSALP), leading to low alkaline phosphatase (ALP) activity. At least 6 clinical forms of HPP have been reported. Certain benign or asymptomatic presentations of HPP in older children may remain undiagnosed, in contrast to severe perinatal and infantile types. The underlying reason of this diagnostic inconsistency may result from unawareness and neglects in labelling and traceability of low ALP levels in laboratories.
Objective: This single center retrospective study was aimed to determine the prevalence of low ALP in children referred to a pediatric hospital throughout one year, relative to medical diagnoses and clinical symptoms. Given the low reference range for ALP may have been omitted, we hypothesized that some individuals with clinical HPP remained underdiagnosed.
Methods: In 853 individuals (382 girls, 471 boys) aged 1 month 18 years, ALP level was measured using the standard colorimetric automatic method with Roche Cobas Integra800 analyzer. As there were no customary algorithm for low reference range for tissue nonspecific ALP levels in our laboratory, we applied the age- and sex-adjusted normative data derived from the previously published reference (1, 2).
Results: The mean level of ALP was 255±192 IU/L (range: 222093). Low ALP was found in 43 children (5%), of which 32 were those aged 411 years. There was no hypophosphatasaemia in neonates/infants within the registry. The main diagnoses associated with low ALP were: acute lymphoblastic leukemia and solid tumors under treatment (n=14), newly diagnosed or exacerbated juvenile idiopathic arthritis (n=9), infections (n=4), traumatic fractures (n=2), while the diagnosis remained undetermined in three cases. Based on the retrospective medical records, four children may have demonstrated symptoms suggesting the features of benign HPP. No case of severe disorder was identified with regard to low ALP.
Conclusions: There is an urgent need to flag the laboratory results of ALP below the normal reference range, although the clinically apparent HPP is regarded a rare disease. Most cases with low ALP are non-characteristic. However, both clinicians and the laboratory staff should be aware that the scoring of low ALP may help identifying individuals with HPP. Further nationwide survey is warranted to determine true and reliable lower cut-off values for ALP in children.
Disclosure: The authors declared no competing interests.
1. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Bird TD, Dolan CR, Stephen K, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1150/. Published November 20, 2007. Updated August 5, 2010. Accessed March 31, 2014.
2. ARUP Laboratories. Alkaline phosphatase isoenzymes, serum or plasma. ARUP Laboratories website. http://ltd.aruplab.com/tests/pub/0021020. Accessed March 31, 2014.