From the Guidelines
Low alkaline phosphatase levels can indicate Wilson disease, a rare genetic disorder that causes copper accumulation in the liver, brain, and other organs [ 1, 1 ].
Key Points
- Low alkaline phosphatase levels can be a hint to suggest Wilson disease in the absence of other indicators 1.
- A high bilirubin to alkaline phosphatase ratio (≥ 2.0) is a reliable indicator of Wilson disease 1.
- Wilson disease should be suspected in patients presenting with acute hepatic failure, Coombs-negative intravascular hemolysis, modest elevations in serum aminotransferases, or low serum alkaline phosphatase 1.
- Low alkaline phosphatase levels can also be seen in other conditions, but Wilson disease is a critical diagnosis to consider due to its potential for severe liver damage and need for prompt treatment 1.
Clinical Considerations
- Patients with low alkaline phosphatase levels should undergo further evaluation for Wilson disease, including measurement of serum ceruloplasmin, urinary copper, and hepatic copper levels 1.
- Early identification and treatment of Wilson disease are critical to prevent liver damage and other complications 1.
From the Research
Low Alkaline Phosphatase Indications
Low alkaline phosphatase (ALP) levels can be an indication of several conditions, including:
- Hypophosphatasia, a rare genetic disorder characterized by low ALP levels and defects in bone and tooth mineralization 2, 3, 4, 5
- Malnutrition, vitamin and mineral deficiencies, and endocrine disorders 3
- Certain medications, such as antiresorptives 3, 4
- Chronic liver disease, although this is a less common finding 6
Clinical Manifestations
The clinical manifestations of low ALP levels can vary, but may include:
- Mild musculoskeletal pain 2
- Tooth loss 2
- Skeletal pain, chondrocalcinosis, calcific periarthritis, and stress fractures 3, 4
- Fatigue, which may be misdiagnosed as chronic fatigue syndrome or fibromyalgia 4
- Dental problems, such as premature tooth loss 4
Diagnostic Approach
The diagnostic approach to patients with low ALP levels may involve:
- Measuring ALP substrates, such as pyrophosphate, pyridoxal phosphate, or phosphoethanolamine 3, 4
- Gene analysis to identify pathogenic variants in the ALPL gene 3, 4, 5
- Imaging studies to evaluate bone mineralization and density 4, 5
- Medical history and physical examination to rule out secondary causes of low ALP levels 3, 5