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Hypophosphatasia: a developmental anomaly of alkaline phosphatase?
Insights
Severe infantile hypophosphatasia in infants showed no detectable leukocyte alkaline phosphatase. Parents had low enzyme levels, while stool and duodenal activity varied, with no significant differences from controls.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Investigates alkaline phosphatase (ALP) in severe infantile hypophosphatasia.
- Examines enzyme activity in affected infants, parents, and controls.
Observation:
- Infants lacked detectable leukocyte ALP; parents showed variable low levels.
- Stool and duodenal ALP varied, with no significant difference in stool activity between patients and controls.
- Therapeutic trials with inducers (phenobarbital, vitamin A, corticosteroid) showed no clinical improvement or rise in serum ALP.
Findings:
- Heterozygous parents had significantly lower ALP than control adults.
- Vitamin A administration increased serum acid phosphatase, suggesting lysosomal effects.
- Tissue ALP analysis revealed variability, with absent activity in some organs and altered electrophoretic patterns in liver and intestinal enzymes.
Implications:
- Highlights the complex biochemical and genetic basis of infantile hypophosphatasia.
- Suggests potential roles for vitamin A in modulating lysosomal activity.
- Underscores the need for further research into diagnostic markers and therapeutic strategies for this severe condition.
Abstract:
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 vivo 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.