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Benign transient hyperphosphatasemia is a condition characterized by greatly increased serum alkaline phosphatase (ALP) without laboratory or clinical evidence of underlying bone or liver disease. It is usually identified incidentally during routine blood testing. We describe the demographic and clinical characteristics of benign transient hyperphosphatasemia in a cohort of healthy infants and children. We performed a retrospective review of electronic medical records on all children aged 1 day to 18 years with a diagnosis of benign transient hyperphosphatasemia, who were registered at 3 central districts in Israel from January 1, 2000, to December 31, 2020. The demographic and clinical characteristics were retrieved from the medical files. The study group comprised 382 infants and children aged from 2 months to 14 years who had serum ALP > 1000 U/L (mean 2557 U/L, range 1002–14,589 U/L). The majority of participants (87%) were aged up to 24 months (median age 14 months, IQR 10–18 months). Fifty-four percent of the study participants were male. In many patients, there was a history of recent fever, gastroenteritis or diarrhea, acute otitis media, and viral infection. A seasonal peak was observed in autumn-early winter, but this may be a detection bias. Conclusion: Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety. What is Known: • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention. What is New: • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety. [ABSTRACT FROM AUTHOR]