What is hypophosphatasia?

Updated: Jun 19, 2020
  • Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
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This autosomal recessive condition, which results in low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), causes rickets without disturbance of calcium and phosphate metabolism. Levels of TNSALP substrates, namely pyridoxal-5'-phosphate (PLP), inorganic pyrophosphate (PPi), and phosphoethanolamine (PEA) in serum and urine, are increased. Clinical severity widely varies, ranging from death in utero to pathologic fractures first presenting only in adulthood.

Six clinical forms of hypophosphatasia have been distinguished, although form assignment may be challenging in some cases. This classification is based on the age at which skeletal lesions are discovered: perinatal (lethal), infantile, childhood, and adult. Two particular forms include odontohypophosphatasia (only biochemical and dental manifestations are present, with no clinical changes in long bones) and pseudohypophosphatasia.

The effects of bone marrow transplant in hypophosphatasia are transient, and bone lesions may recur 6 months after the transplant. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used in patients with childhood hypophosphatasia with some clinical improvement.

The US Food and Drug Administration has approved asfotase alfa as the first permitted treatment for perinatal, infantile and juvenile-onset hypophosphatasia. [9]  A study by Whyte et al found that asfotase alfa enzyme replacement therapy is effective and safe for treating children with hypophosphatasia. [10]

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