From the Guidelines
Low alkaline phosphatase (ALP) levels can be a hint to suggest Wilson disease in the absence of other indicators, and a high bilirubin to alkaline phosphatase ratio is a reliable albeit indirect indicator of Wilson disease. According to the AASLD position paper on the management of acute liver failure 1, very low serum alkaline phosphatase or uric acid levels are hints to suggest Wilson disease. This condition is an uncommon cause of acute liver failure (ALF), but early identification is critical because the fulminant presentation of Wilson disease is considered to be uniformly fatal without transplantation. Some key points to consider in the context of low ALP levels include:
- Wilson disease typically occurs in young patients, accompanied by the abrupt onset of hemolytic anemia with serum bilirubin levels > 20 mg/dL
- Serum ceruloplasmin is typically low, but may be normal in up to 15% of cases
- High serum and urinary copper levels as well as hepatic copper measurement may confirm the diagnosis
- Renal function is often impaired as the released copper can cause renal tubular damage
- Treatment to acutely lower serum copper and to limit further hemolysis should include albumin dialysis, continuous hemofiltration, plasmapheresis or plasma exchange, rather than initiation of treatment with penicillamine 1.
From the Research
Low Alkaline Phosphatase (ALP) Levels
- Low ALP levels can be associated with hypophosphatasia, a rare disease characterized by diverse musculoskeletal symptoms 2
- Hypophosphatasia can cause debilitating physical conditions that severely affect quality of life, and a better comprehension of adult forms of the disease is essential to reduce delay in diagnosis and ensure suitable management 2
Relationship with Other Conditions
- Low ALP levels can also be seen in patients with kidney bone disease, which includes bone disorders, mineral disarrays, and vascular calcification 3
- In contrast, elevated ALP levels are typically seen in osteomalacia, a disorder of bone metabolism leading to reduced bone mineralization 4, 5
Nutritional Intake and Bone Health
- Adults with probable undiagnosed celiac disease had lower bone density than adults without the disease, despite reporting higher total calcium intake and nutritional density of both calcium and phosphorus 6
- No differences in serum calcium, vitamin D, or alkaline phosphatase levels were observed between adults with and without probable undiagnosed celiac disease 6
Clinical Assessment and Management
- A schematic approach to hypophosphatasia evaluation and management is essential to ease its recognition and diagnosis, and to reduce delay in diagnosis and ensure suitable management 2
- The management of kidney bone disease and related conditions, such as hyperparathyroidism and vitamin D deficiency, is critical to improving patient survival and other clinical outcomes 3