From the Guidelines
Low alkaline phosphatase (ALP) levels can be caused by Wilson's disease, among other conditions, as indicated by very low serum alkaline phosphatase levels being a hint to suggest Wilson disease in the absence of other indicators 1. When considering the causes of low ALP levels, it's essential to evaluate the clinical context and potential underlying conditions. Some key factors to consider include:
- Genetic disorders like hypophosphatasia, which can lead to chronically low ALP levels
- Medical conditions such as hypothyroidism, pernicious anemia, celiac disease, and severe anemia
- Conditions affecting bone metabolism like osteoporosis and vitamin D deficiency
- Certain medications that can reduce ALP levels, including antibiotics, antiepileptics, and oral contraceptives
- Nutritional deficiencies, such as malnutrition, protein deficiency, zinc deficiency, magnesium deficiency, and vitamin B6 deficiency According to the AASLD position paper on the management of acute liver failure, Wilson's disease is a significant consideration in cases of low ALP levels, particularly in young patients with hemolytic anemia and elevated bilirubin levels 1. The presence of very low serum alkaline phosphatase levels, along with other indicators like a high bilirubin to alkaline phosphatase ratio, can suggest Wilson's disease as a potential cause of low ALP levels 1.
From the Research
Causes of Low Alkaline Phosphatase (ALP) Levels
- Hypophosphatasia (HPP), a rare genetic disorder characterized by impaired mineralization of bones and teeth, is a primary cause of low ALP levels 2, 3, 4, 5
- Mutations in the ALPL gene, which encodes tissue non-specific ALP, can lead to HPP and low ALP levels 2, 3, 5
- Vitamin and mineral deficiencies, such as zinc and vitamin D deficiency, may contribute to low ALP levels 6
- Malnutrition and endocrine disorders can also cause low ALP levels 5
- Certain medications, including antiresorptives, can lead to low ALP levels 4, 5
- Acquired disorders, such as liver disease, can also result in low ALP levels 5
Biochemical Markers of Low ALP Levels
- Low bone-specific ALP levels can be a marker of HPP, even in the presence of normal total ALP levels 2
- Elevated levels of pyridoxal phosphate (PLP) and phosphoethanolamine (PEA) can be associated with low ALP levels 3
- Low ALP levels can be inversely correlated with serum calcium, PLP, and PEA levels 3
Diagnostic Approach to Low ALP Levels
- Measuring ALP substrates, such as pyrophosphate, PLP, or PEA, can help establish enzyme deficiency 5
- Gene analysis showing a pathogenic variant in ALPL can confirm the diagnosis of HPP 2, 3, 5
- A diagnostic approach that considers multiple factors, including clinical presentation, biochemical markers, and genetic analysis, is necessary to accurately diagnose the cause of low ALP levels 5