From the Guidelines
Hyperphosphatasemia is primarily caused by conditions affecting the liver and bone, with elevated alkaline phosphatase (ALP) levels being a hallmark of these conditions.
Causes of Hyperphosphatasemia
- Liver conditions: Cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis, can lead to elevated ALP levels 1.
- Bone conditions: Bone disease, such as Paget’s disease, bony metastases, or fracture, can also cause elevated ALP levels 1.
- Other conditions: Elevated ALP levels can also be seen in conditions such as congestive heart failure, hepatic congestion, and ischemic cholangiopathy 1.
Diagnostic Considerations
- GGT measurements: Concomitantly elevated gamma-glutamyl transpeptidase (GGT) can help confirm that an elevated ALP originates from the liver and indicates cholestasis 1.
- Imaging: Imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis 1.
Clinical Context
- X-linked hypophosphataemia (XLH): Although XLH is characterized by hypophosphataemia, elevated ALP levels are also a biochemical hallmark of this condition 1.
- Physiological variations: ALP levels are physiologically higher in childhood, associated with bone growth, and in pregnancy, due to placental production 1.
From the Research
Causes of Hyperphosphatasemia
The causes of hyperphosphatasemia are not fully understood, but several studies have shed some light on the possible factors contributing to this condition.
- Transient hyperphosphatasemia is a benign condition characterized by a rapid rise and fall in plasma alkaline phosphatase (ALP) activity without biochemical or clinical evidence of underlying bone or liver disease 2, 3, 4, 5, 6.
- It is often identified incidentally during routine blood testing, and its pathogenesis is likely to be multifactorial 6.
- Viral etiology has been proposed as a possible cause, with transiently increased bone turnover and impaired clearance of ALP from the serum also considered as potential factors 6.
- Recent fever, gastroenteritis or diarrhea, acute otitis media, and viral infection have been reported in many patients with benign transient hyperphosphatasemia 4.
- The condition is usually seen in infants and children, but rare cases have been reported in adults, including a complicated multiorgan adult transplant patient 3.
Characteristics of Hyperphosphatasemia
The characteristics of hyperphosphatasemia include:
- Greatly increased serum alkaline phosphatase (ALP) without laboratory or clinical evidence of underlying bone or liver disease 2, 4.
- The condition is usually benign and resolves spontaneously, with no intervention required 4, 6.
- A seasonal peak has been observed in autumn-early winter, but this may be a detection bias 4.
- The majority of patients are aged up to 24 months, with a median age of 14 months 4.
Diagnosis and Management
The diagnosis and management of hyperphosphatasemia involve:
- Repeating the alkaline phosphatase level within a few months to confirm the resolution of the condition 4.
- Excluding other known causes of markedly elevated serum ALP, especially bone and liver disease 4, 5.
- A "wait and see" approach is optimal to avoid unnecessary investigations and parental anxiety 4.