benign transient hyperphosphatasia

Last reviewed 10/2023

Benign transient hyperphosphatasia (BTH)

• a disorder characterised by transient marked increases in alkaline phosphatase (ALP) activity in the absence of bone or liver disease
  • first reported as a condition occurring in infancy and early childhood only
    • occurs most commonly in infants and children younger than five years of age. A few adults with similar patterns have been reported (1)
      
      
  • aetiology unclear
    • theories put forward to explain the transient rise in ALP activity include:
      • increased hepatic ALP synthesis as part of the acute phase reaction
        • reflecting infectious diseases have accompanied some cases of BTH
        • however, BTH has also been observed in healthy subjects and during the course of a wide variety of clinical disorders
      • decreased clearance of ALP from circulation due to increased sialation of the enzyme is the most probable mechanism
        • cause of the altered sialation in BTH remains uncertain
          • supported by the abnormal sialation of liver and bone isoenzyme fractions (2)
            
            
  • prevalence of BTH in infants is unknown
    • in 1966, Asanti et al studied ALP in 260 healthy infants and 1.5% had an unexplained transient rise in ALP activity to more than 3 times the upper reference limit (URL) for the assay
    • Parker studied a population of 204 adults in the acute medical setting and found that 32% of the cases of hyperphosphatasia were attributed to BTH
      • note that in these cases the elevation in ALP was less than three times the upper reference limit

Increased ALP activity in BTH can vary from 3 to 53 times URL of adults (5):

• variability may be attributed to the timing of the ALP sample in relation to the peak ALP activity
• Serum ALP levels gradually return to normal within two to three months but have persisted as long as six months in a few cases (6)

In series reporting the results of long-term follow-up, no clinical sequelae were noted up to four years after the episode of transient hyperphosphatasia (7)

If BTH is suspected, it is important to request ALP isoenzyme analysis by electrophoresis as this is the only method that can identify the electrophoretic pattern of ALP isoenzymes that is diagnostic of BTH (4)

• electrophoretic isoenzyme pattern consists of two bands of increased activity
  • a band of a homogenous compact appearance with biochemical characteristics of liver origin but with enhanced anodal mobility
  • second diffuse band with characteristics and mobility of bone ALP
• diagnosis
  • confirmed by the ALP activity and/or electrophoresis isoenzyme pattern returning to normal within 3-4 months

Reference:

• Rosalki SB, Foo AY, Went J, Williams R, Baker DM. Transient hyperphosphatasemia of infancy and childhood" in an adult. Clin Chem. 1991;37(6):1137.
• Crofton PM. What is the cause of benign transient hyperphosphatasemia? A study of 35 cases. Clin Chem 1988; 34: 335-40
• Asanti R, Hutin H, Visakorpi JK. Serum alkaline phosphates in healthy infants, occurrence of abnormally high values without known cause. Ann Paediatr Fenn 1966; 12: 139.
• Parker SG. Transient hyperphosphatasaemia in association with acute infection in adults. Postgrad Med J 1991; 67: 638-42
• Jassam NJ et al. Transient rise in alkaline phosphatase activity in adults. BMJ Case Rep. 2009
• Carroll AJ, Coakley JC.Transient hyperphosphatasaemia: an important condition to recognize. J Paediatr Child Health. 2001;37(4):359.
• Steinherz PG, Steinherz LJ, Nisselbaum JS, Murphy ML. Transient, marked, unexplained elevation of serum alkaline phosphatase. JAMA. 1984;252(23):3289.