Hypophosphotasia (HPP)

Hypophosphatasia (HPP) is a rare genetic disorder, which affects the development of bones and teeth. Normal mineralisation is a process by which calcium and phosphorous are deposited in developing bones and teeth which is important for strong bones and rigid teeth. Individuals with HPP have trouble making an enzyme called alkaline phosphatase (ALP) due to a faulty gene (ALPL gene), which causes defective mineralisation, preventing calcium and phosphorous from binding together and depositing in the bones. Due to the defective mineralisation, bones may become soft, leading to bony deformities and increased risk of sustaining fractures. Teeth may become loose and fall out prematurely and many individuals experience generalised pain/fatigue.

Signs and symptoms

Signs and symptoms for HPP can vary widely and appear from before birth to adulthood. It is recognised that the severity of HPP usually reflects the patients’ age when symptoms appear. The more severe forms tend to occur before birth and in early infancy. Diagnosis can be made through blood tests and radiological investigations and confirmed by genetic testing.

Benign Perinatal HPP

  • Usually detected on foetal ultrasound while in utero
  • Short and bowed limbs
  • Skeletal deformities resolve spontaneously during later stages of pregnancy or after birth

Perinatal HPP

  • Apparent at birth
  • Most severe type with life threatening complications
  • Likely association with breathing difficulties and fits
  • Usually short limbs, abnormal chest shape and soft skull bones

Infantile HPP

  • Diagnosed after birth but before 6 months of age
  • Infantile form is often more severe than childhood HPP
  • Skeletal deformities as a result of weak and soft bones
  • Can be associated with respiratory complications
  • Poor feeding and slow weight gain
  • May have elevated calcium levels in the blood stream resulting in vomiting and kidney problems

Childhood HPP

  • Usually less severe than infants
  • Premature tooth loss can often be one of the first signs of HPP
  • Can present with delay in motor developmental milestones
  • May have short stature
  • May shows signs of bowed legs or knock-knees and abnormal skull shape

Adulthood HPP

  • Usually becomes apparent in middle age and often misdiagnosed as osteoporosis
  • Associated with softening of bones and increased risk of fractures
  • Adults often present with pain and swelling of joints
  • May lose their secondary teeth prematurely
  • This is not considered as a lethal form of HPP

Odontohypophosphatasia HPP

  • Mildest form of HPP
  • Affects only the teeth – the bones appear healthy
  • Premature loss of teeth occurs during childhood
  • Individuals experience abnormal tooth development


Historically treatment was aimed at managing the symptoms individuals with HPP present with.

Bone targeted enzyme replacement therapy (Strensiq) for the treatment of pediatric-onset HPP was approved through national funding agreement with the National Institute for Health and Care Excellence (NICE) and NHS England in 2017. The Managed Access Agreement (MAA) provides access to Strensiq (Asoftase Alfa) for patients in England with paediatric on-set HPP.

The MAA was developed in collaboration with physicians, thought-leaders, patient groups, NHS England, and Alexion to ensure access to Strensiq for infants, children and adult patients with pediatric-onset HPP who experience the most disabling symptoms and are expected to see beneficial outcomes with Strensiq use.


It is advised that individuals with HPP are managed by a multi-disciplinary team with understanding and knowledge of HPP. Physiotherapy and occupational therapy input is paramount to manage pain, strengthen muscle and bone, promote independence and manage daily living tasks. Dental care and hygiene is equally important and therefore regular dental input from a specialist dentist is also recommended.

We are very thankful to Jas Kaur Sahota and Dr Vrinda Saraff for their help with compiling this information

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