Transient hyperphosphatasemia of infancy and early childhood
- Rima Fawaz, MD
Rima Fawaz, MD
- Instructor in Pediatrics
- Harvard Medical School
- Esther Israel, MD
Esther Israel, MD
- Assistant Professor of Pediatrics
- Harvard Medical School
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 . 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 .
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 , Epstein-Barr virus , and human immunodeficiency virus (HIV) ; following liver [9-11] or kidney transplant ; and in children on cyclosporine  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 . 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].
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