Transient hyperphosphatasemia of infancy and early childhood: clinical and biochemical features of 21 cases and literature review.

Abstract

Clinical and biochemical features of transient hyperphosphatasemia of infancy and early childhood are reviewed in 21 patients we have studied and in a further 93 cases reported in the literature. The diagnosis is suggested by the finding of an increased activity of alkaline phosphatase (EC 3.1.3.1) in plasma, typically more than fivefold the adult upper reference limit, in a child under five years of age, without evidence of liver or bone disease. The condition is confirmed by the presence of a characteristic pattern of alkaline phosphatase isoenzymes and by the normalization of the enzyme's activity in plasma within approximately three months. The etiology of the condition and possible mechanisms of the enzyme increase are discussed.

Transient hyperphosphatasemia in children revisited

“…The length of abnormal ALP values and the benign outcome of our patients are similar to what is reported in the literature. 3,4,6,10,11,14,17,21,29 2 years of age or younger, which is also consistent with the literature. 5,7,10,11,13,16,19 The main limitation of the study is its retrospective nature which limited our ability to control the clinical investigation and ensure appropriate follow-up and timing of laboratory studies.…”

“…These finding are consistent with previous studies and support the theory of an infectious agent as a possible etiology for TH. 4,14,15,[18][19][20][21] Mahy et al have shown that Riley virus-infected mice decrease enzyme clearance probably through the inhibition of the reticuloendothelial system. 22 Nevertheless, this decreased enzyme clearance has not been shown for ALP.…”

“…Others, however, did not find evidence for a specific agent. 11,14,17,19,21 Still, although we did not systematically test for the presence of an infectious agent (only one patient was diagnosed with cytomegalovirus infection), infectious agents are unlikely to explain all of the features of TH.…”

“…Once the ALP values had returned to normal, the liver isoenzyme mobility normalized. 11,14,15 Experiments showed that it was ascribable to excess sialic acid residues. Unlike the sialic acid attached to the normal liver isoenzyme, the sialic acid present in TH liver ALP was readily removable and normalized by very brief incubation with sialidase.…”

“…14 This sialic acid excess may affect ALP clearance and have been attributed to certain drugs especially anticonvulsants. 14,15,28 Only four of the children in our study were on chronic drugs. Two were on valproic acid, one on griseofulvin and one on inhaled budesonide and terbutaline.…”