Is an alkaline phosphatase (ALP) level of 24 considered high?

Alkaline Phosphatase Level of 24 is LOW, Not High

A level of 24 for alkaline phosphatase is not high but actually significantly low, which may indicate hypophosphatasia or other conditions requiring further evaluation. 1

Understanding Alkaline Phosphatase Reference Ranges

According to clinical guidelines, alkaline phosphatase (ALP) levels are considered elevated when:

• ≥2 times the upper limit of normal (ULN) 1
• Particularly concerning when accompanied by elevated gamma-glutamyl transpeptidase (GGT) in the absence of bone disease

In contrast, low ALP levels (below the age/gender-specific reference range) are not typically flagged by laboratories as abnormal 2, despite their potential clinical significance.

Clinical Significance of Low ALP

Potential Causes of Low ALP

• Genetic causes:

  • Hypophosphatasia (HPP) - most common genetic cause due to pathogenic variants in the ALPL gene 3
  • Present in approximately 50% of adults with unexplained low ALP 4

• Acquired causes:

  • Malnutrition
  • Vitamin and mineral deficiencies
  • Endocrine disorders
  • Medication effects (including antiresorptives)
  • Severe acute injuries or diseases 3

Clinical Manifestations

Patients with low ALP may present with:

• Mild musculoskeletal pain
• Tooth loss (more common in those with ALPL mutations - 48% vs 12%) 4
• Adult forms of hypophosphatasia may include:
  • Skeletal pain
  • Chondrocalcinosis
  • Calcific periarthritis
  • Dental problems
  • Stress fractures 3

Diagnostic Approach for Low ALP

1. Confirm persistently low levels:

   • Repeat testing to ensure the finding is consistent
   • Note that liver disease can sometimes mask low ALP by causing elevation 5

2. Laboratory assessment:

   • Measure ALP substrates:
     • Pyridoxal phosphate (PLP)
     • Pyrophosphate
     • Phosphoethanolamine (PEA) 3
   • Check serum calcium and phosphate levels (hyperphosphatemia and hypercalcemia may be present) 4

3. Genetic testing:

   • Consider ALPL gene analysis if clinical suspicion for hypophosphatasia exists 3
   • Missense mutations are most common (86%) 4

Clinical Implications

Interestingly, patients with chronic liver disease who have consistently low ALP levels may show less biochemical evidence of active disease, with lower serum aminotransferase and bilirubin levels 6. However, this finding requires further investigation.

Important Caveat

Unlike elevated ALP levels, which are routinely flagged by laboratories as abnormal, low ALP levels are commonly not flagged, potentially leading to delayed or missed diagnosis of conditions like hypophosphatasia 2. This is particularly concerning as effective treatments for conditions like HPP are now available.

Recommendation

For a patient with an ALP level of 24:

1. Confirm the finding with repeat testing
2. Assess for clinical manifestations associated with low ALP
3. Consider measuring ALP substrates (PLP, PEA)
4. Consider genetic testing for ALPL mutations if clinically indicated
5. Evaluate for other causes of low ALP including nutritional and endocrine disorders

This approach will help determine the clinical significance of this laboratory finding and guide appropriate management.