Hypophosphatasia: A developmental anomaly of alkaline phosphatase?

Rafael Gorodischer, Ronald G. Davidson, Luis L. Mosovich, Sumner J. Yaffe

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24 Scopus citations


This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 ± 9.77 U) and control infants (40.55 ± 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 ± 0.47 as compared with 19.10 ± 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other. Three “inducers” of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting an in viva action of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum. Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both. Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient’s liver enzyme corresponded to the newborn’s fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age-matched control subjects. Among the many quantitative and qualitative alterations in alkaline phosphatases found in these two infants with the severe form of hypophosphatasia, the most striking finding was the presence in the liver of one of the cases of what appeared to be a form of the enzyme normally present only during very early postnatal life. The defective regulation of the various alkaline phosphatase isozymic forms during development may thus represent the basic defect in this disease.

Original languageEnglish
Pages (from-to)650-656
Number of pages7
JournalPediatric Research
Issue number7
StatePublished - 1 Jan 1976
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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