Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Transient hyperphosphatasemia of infancy and early childhood

Rima Fawaz, MD
Esther Israel, MD
Section Editor
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD


Transient hyperphosphatasemia (TH) of infancy and early childhood is characterized by a marked elevation of serum alkaline phosphatase in the absence of detectable liver or bone disease, with a return to normal levels within weeks or months. Because the condition is thought to be benign, it is also called benign TH. Recognition of this phenomenon permits avoidance of unnecessary procedures and concerns, provided that underlying liver and bone disease are appropriately excluded.

The clinical presentation and evaluation of an infant or young child with marked elevation of serum alkaline phosphatase will be reviewed here. Evaluation of an older child or adult with elevated alkaline phosphatase, or of any individual with elevations of multiple liver enzymes, is discussed separately. (See "Enzymatic measures of cholestasis (eg, alkaline phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase)" and "Approach to the patient with abnormal liver biochemical and function tests".)


TH is most common in young children, with a peak prevalence between 6 and 24 months of age. In a cohort of 316 healthy children younger than two years of age, alkaline phosphatase levels >1000 U/L (2.5 times the upper limit of normal) were found in 2.8 percent [1]. More moderate elevations of alkaline phosphatase (between 400 and 1000 U/L) were found in 5.1 percent of the subjects. A slightly higher prevalence rate was found in a Swedish study in healthy children aged 6 months to 18 years. Elevated serum alkaline phosphatase levels >1000 U/L were noted in 6 of 699 children, all of whom were between 7 and 22 months of age. Hence, the prevalence of TH in the age group from six months to two years was 6.2 percent. None of the children older than two years had serum alkaline phosphatase levels >1000 U/L [2].

Most children with TH are healthy. Some reports suggest an association of TH with a variety of clinical conditions, including gastroenteritis, respiratory infection, failure to thrive, and asthma. TH has also been reported in association with viral infections such as respiratory syncytial virus [3-5], enteroviruses [6], Epstein-Barr virus [7], and human immunodeficiency virus (HIV) [8]; following liver [9-11] or kidney transplant [9]; and in children on cyclosporine [12] or chemotherapy for leukemia and lymphoma [13,14]. Some of these apparent disease associations may reflect more frequent laboratory testing to monitor the underlying disease. Indeed, in the largest study that prospectively evaluated a healthy population of infants and toddlers, no association with failure to thrive or other growth parameters was found [1]. A seasonal distribution of cases has been noted in some series, with more cases identified in late summer and early fall [13,15].


TH is usually identified as an incidental finding when an isolated elevation in serum alkaline phosphatase is noted during laboratory testing for routine health care, or as part of an evaluation for a specific complaint. TH occurs most commonly in infants and children younger than five years of age. A few adults with similar patterns have been reported [16-21]. The serum alkaline phosphatase concentration is typically elevated four to five times the upper reference limit but elevations up to 20 times the pediatric upper reference limit (or about 50 times the adult upper reference limit) have been described [15,21-23]. In most cases there are elevations in both liver and bone alkaline phosphatase isoenzymes, and (rarely) in intestinal alkaline phosphatase isoenzymes [15,24].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 04, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Huh SY, Feldman HA, Cox JE, Gordon CM. Prevalence of transient hyperphosphatasemia among healthy infants and toddlers. Pediatrics 2009; 124:703.
  2. Ridefelt P, Gustafsson J, Aldrimer M, Hellberg D. Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels. Horm Res Paediatr 2014; 82:399.
  3. Goto M. [Is respiratory syncytial virus one of the causative agents for transient hyperphosphatasemia?]. Rinsho Byori 2002; 50:1146.
  4. Holt PA, Steel AE, Armstrong AM. Transient hyperphosphatasaemia of infancy following rotavirus infection. J Infect 1984; 9:283.
  5. Schönau E, Herzog KH, Böhles HJ. Transient hyperphosphatasaemia of infancy. Eur J Pediatr 1988; 148:264.
  6. Suzuki M, Okazaki T, Nagai T, et al. Viral infection of infants and children with benign transient hyperphosphatasemia. FEMS Immunol Med Microbiol 2002; 33:215.
  7. Koike Y, Aoki N. Benign transient hyperphosphatasemia associated with Epstein-Barr virus infection. Pediatr Int 2013; 55:667.
  8. Fennoy I, Laraque D. Benign transient hyperphosphatasia and HIV infection. Clin Pediatr (Phila) 1989; 28:180.
  9. Ranchin B, Villard F, André JL, et al. Transient hyperphosphatasemia after organ transplantation in children. Pediatr Transplant 2002; 6:308.
  10. Arikan C, Arslan MT, Kilic M, Aydogdu S. Transient hyperphosphatasemia after pediatric liver transplantation. Pediatr Int 2006; 48:390.
  11. Yoshimaru K, Matsuura T, Hayashida M, et al. Transient hyperphosphatasemia after pediatric liver transplantation. Pediatr Int 2016; 58:726.
  12. Mori T, Tanaka R, Nishida K, et al. Transient hyperphosphatasemia in three pediatric patients treated with cyclosporine. Pediatr Int 2016; 58:429.
  13. Crofton PM. What is the cause of benign transient hyperphosphatasemia? A study of 35 cases. Clin Chem 1988; 34:335.
  14. Massey GV, Dunn NL, Heckel JL, et al. Benign transient hyperphosphatasemia in children with leukemia and lymphoma. Clin Pediatr (Phila) 1996; 35:501.
  15. Behúlová D, Bzdúch V, Holesová D, et al. Transient hyperphosphatasemia of infancy and childhood: study of 194 cases. Clin Chem 2000; 46:1868.
  16. Rosalki SB, Hurst NP. Transient presence in serum of an atypical alkaline phosphatase. Clin Chim Acta 1976; 73:149.
  17. Schambeck CM, Kopp A, Mora-Maza G, Keller F. Transient alkaline hyperphosphatasaemia in an adult: biochemical peculiarities. Eur J Clin Chem Clin Biochem 1997; 35:441.
  18. Rosalki SB, Foo AY, Went J, et al. "Transient hyperphosphatasemia of infancy and childhood" in an adult. Clin Chem 1991; 37:1137.
  19. Onica D, Torssander J, Waldenlind L. Recurrent transient hyperphosphatasemia of infancy in an adult. Clin Chem 1992; 38:1913.
  20. Ilham MA, Cookson A, Dheerendra S, et al. Idiopathic severe elevation of serum alkaline phosphatase following adult renal transplantation: case reports. Transplant Proc 2008; 40:2059.
  21. Gualco G, Lava SA, Garzoni L, et al. Transient benign hyperphophatasemia. J Pediatr Gastroenterol Nutr 2013; 57:167.
  22. Stein P, Rosalki SB, Foo AY, Hjelm M. Transient hyperphosphatasemia of infancy and early childhood: clinical and biochemical features of 21 cases and literature review. Clin Chem 1987; 33:313.
  23. Rosalki SB, Foo Y. Transient hyperphosphatasemia of infancy: four new cases, and a suggested etiology. Clin Chem 1980; 26:1109.
  24. Kruse K, Kracht U. [Isolated elevation of serum alkaline phosphatase]. Dtsch Med Wochenschr 1985; 110:669.
  25. Cabrera-Abreu JC, Green A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem 2002; 39:22.
  26. Tolaymat N, de Melo MC. Benign transient hyperphosphatasemia of infancy and childhood. South Med J 2000; 93:1162.
  27. Garrote de Marcos JM, Molina Arias M, Echávarri Olvarría F, Arregui Sierra A. [Benign transient hyperphosphatasemia: the contribution of 20 new cases]. An Esp Pediatr 1996; 44:112.
  28. Carroll AJ, Coakley JC. Transient hyperphosphatasaemia: an important condition to recognize. J Paediatr Child Health 2001; 37:359.
  29. Steinherz PG, Steinherz LJ, Nisselbaum JS, Murphy ML. Transient, marked, unexplained elevation of serum alkaline phosphatase. JAMA 1984; 252:3289.
  30. Posen S, Lee C, Vines R, et al. Transient hyperphosphatasemia of infancy--an insufficiently recognized syndrome. Clin Chem 1977; 23:292.