Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)


Synonym(s) HPP
Rathburn disease
Prevalence Unknown
Inheritance Autosomal dominant
or Autosomal recessive
Age of onset All ages
  • E83.3
  • C0020630
  • D007014
  • 10049933


Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity.

The prevalence of severe forms of the disease has been estimated at 1/100 000.

The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms. Depending on the age at diagnosis, six clinical forms are currently recognized: perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. In the lethal perinatal form, the patients show markedly impaired mineralization in utero. In the prenatal benign form, these symptoms are spontaneously improved. Clinical symptoms of the infantile form are respiratory complications, premature craniosynostosis, widespread demineralization, and rachitic changes in the metaphyses. The childhood form is characterized by skeletal deformities, short stature, and waddling gait, and the adult form by stress fractures, thigh pain, chondrocalcinosis, and marked osteoarthropathy. Odontohypophosphatasia is characterized by premature exfoliation of fully rooted primary teeth and/or severe dental caries, often not associated with abnormalities of the skeletal system.

The disease is due to mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding the tissue-nonspecific alkaline phosphatase (TNAP).

The diagnosis is based on laboratory assays and DNA sequencing of the ALPL gene. Serum alkaline phosphatase (AP) activity is markedly reduced in hypophosphatasia, while urinary phosphoethanolamine (PEA) is increased. By using sequencing, approximately 95% of mutations are detected in severe (perinatal and infantile) hypophosphatasia.

Prenatal assessment of severe hypophosphatasia by mutation analysis of chorionic villus DNA is possible.

Genetic counseling of the disease is complicated by the variable inheritance pattern (autosomal dominant or autosomal recessive), the existence of the uncommon prenatal benign form, and by incomplete penetrance of the trait.

There is no curative treatment for hypophosphatasia, but symptomatic treatments such as non-steroidal anti-inflammatory drugs or teriparatide have been shown to be of benefit. Enzyme replacement therapy will be certainly the most promising challenge of the next few years.

Expert reviewer(s)

  • Etienne MORNET

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Review article
  • EN (2007)
Guidance for genetic testing
  • EN (2013,pdf)
Article for general public
Clinical genetics review
  • EN (2011)
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.