hypophosphatasia

Last reviewed 01/2018

Hypophosphatasia is an inherited defect in alkaline phosphatase activity. The consequence may be a disease disease similar to rickets.

• hypophosphatasia is a rare inherited disorder characterised by low levels of serum alkaline phosphatase with a spectrum of skeletal defects
  • classified into different clinical types:
    • perinatal
    • infantile
    • childhood
    • adult
    • pseudo-hypophosphatasia
    • odontohypophosphatasia in which only the teeth are affected
      
      
    • in its severest form death may occur in utero from skeletal malformation (perinatal hypophosphatasia) while in its mildest form, the adult type, there may be very minor or no skeletal defects
      
      
  • severe forms of hypophosphatasia (perinatal and infantile) are inherited as autosomal recessive (1)
    
    
  • less severe adult type may be inherited as autosomal dominant (1)

The incidence of the severe forms is estimated in 1/100000 (USA), but because its incomplete penetrance it is difficult to know the correct prevalence (2)

Hypophosphatasia results from a defective production of alkaline phosphatase as a result of mutations in the tissue non specific alkaline phosphatase (TNSALP) gene

Biochemical diagnosis of hypophosphatasia is made on a combination of low serum alkaline phosphatase levels and abnormal levels of phosphorylated metabolites

• where available, DNA analysis for mutations in the TNSALP gene has been used to confirm the diagnosis of hypophosphatasia

Notes:

• leucocytes express alkaline phosphatase activity
  • altered levels of which have been used in a variety of haematological disorders
  • in hypophosphatasia the leucocyte alkaline phosphatase (LAP) score has been reported to be low in hypophosphatasia

Reference:

• M.P. Whyte Hypophosphatasia ,in: C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, J.B. Stanbury, J.B. Wyngaarden, D.S. Fredrickson (Eds.), The metabolic and molecular bases of inherited disease (7th ed), Vol. 4McGraw-Hill, New York (1995), 4095-4411
• Mornet E, Nunes ME. Hypophosphatasia. Gene Reviews - NCBI Bookshelf 2010. 1-16.
• W.R. Beisel, N. Benjamin, K.F. Austen Absence of leukocyte alkaline phosphatase activity in hypophosphatasia Blood 1959;14:975-977