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Transient Benign Hyperphophatasemia

Gualco, Gianluca*; Lava, Sebastiano A.G.*; Garzoni, Luca*; Simonetti, Giacomo D.; Bettinelli, Alberto; Milani, Gregorio P.§; Provero, Maria Cristina; Bianchetti, Mario G.*

Journal of Pediatric Gastroenterology and Nutrition: August 2013 - Volume 57 - Issue 2 - p 167–171
doi: 10.1097/MPG.0b013e3182922807
Original Articles: Hepatology and Nutrition

Background and Aim: Sometimes, a temporary increase in alkaline phosphatase level is found in healthy infants and toddlers without evidence of liver or bone disease. The condition is customarily termed transient benign hyperphosphatasemia of infancy and early childhood. Most textbooks do not refer to the condition. The aim of the study was to promote broader awareness of transient benign hyperphosphatasemia.

Methods: We completed a systematic review of the literature using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.

Results: The 142 reports retained for analysis included 813 cases (male:female ratio 1.1:1.0): 80 in subjects older than 18 years and 733 in subjects 18 years or younger. The alkaline phosphatase ratio, calculated by dividing the measured level by the upper limit of normal, was ≥5.0 in ≈70% and the duration of the elevation was ≤4 months in 80% of the cases. Transient benign hyperphosphatasemia often followed a benign infection, but available data fail to demonstrate a causal link. The prevalence of transient benign hyperphosphatasemia ranged from 1.1% to 3.5% in infants 2 to 24 months of age.

Conclusions: Transient benign hyperphosphatasemia is likely the most common cause of hyperphosphatasemia among healthy infants and toddlers. Sometimes it also occurs in older children and adults, indicating that the traditional term transient benign hyperphosphatasemia of infancy and early childhood may not be correct. The elevation in alkaline phosphatase persists for >4 months in ≈20% of the cases. Recognition of this benign condition is crucial to avoid unnecessary investigations.

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*Integrated Department of Pediatrics, Ente Ospedaliero Cantonale Ticinese, and University of Bern

Pediatric Nephrology, University Children's Hospital Bern and University of Bern, Bern, Switzerland

Division of Pediatrics, San Leopoldo Mandic Hospital, Merate-Lecco, Italy

§Pediatric Emergency Unit, Clinica De Marchi, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.

Address correspondence and reprint requests to Mario G. Bianchetti, MD, San Giovanni Hospital, 6500 Bellinzona, Switzerland (e-mail:

Received 14 January, 2013

Accepted 14 March, 2013

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The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,