Every now and then I see a low alkaline phosphatase (ALP)–usually this is an inconsequential finding.  A recent study (V Saraff et al. J Pediatr 2016; 172: 181-6) provides insight into this problem.

In a retrospective study spanning 8 years, the authors identified 1526 samples from 323,064 which had an ALP <100 U/L.  Most of these were transient.  Only 18 were identified as having persistently low ALP.  In this group, 13 were tracked down. In this group, among four who had ongoing low ALP, two had mutations in the ALPL gene.

The authors propose, in Figure 3, how to manage a low ALP.  In those with an accurate ALP (not a degraded blood sample) and who were not chronically ill, they suggest looking for symptoms of hypophosphatasia:

• respiratory failure
• vitamin B6 responsive seizures
• elevated calcium, phosphate and/or nephrocalcinosis
• failure to thrive/short stature
• fractures/bone pain
• craniosynostosis
• chest deformity
• delayed walking, waddling gait
• premature loss of teeth/late dentition

In those with likely hypophosphatasia, confirm with a pyridoxal-5′-phosphate and urinary phosphoethanolamine. If these are normal, hypophosphatasia is unlikely.  If these are elevated, the next step per the authors would be checking knee, lateral/AP skull.  If these are suggestive, then undergoing genetic testing is recommended or seeing a bone specialist.

In those with those who do not have symptoms of hypophosphatasia, the authors recommend checking for other causes.  Workup could include zinc, magnesium, thyroid function, blood counts, renal/liver assays, parathyroid hormone, vitamins B12/C/D, celiac serology, and ceruloplasmin.

My take: In those with persistently low alkaline phosphatase, keep this reference handy.

Related blog post (for high alkaline phosphatase): We still see this

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