Hypophosphatasia

Also known as HPP

What Causes HPP?

The enzyme Alkaline Phosphate or ALP is mutated in people with HPP, resulting in low amounts of ALP. ALP lets calcium and phosphate bind together to form healthy bones. People with HPP cant bone build properly because phosphate and calcium cannot mineralize.

What is Affected By HPP

Chromosome 1 is affected by HPP. ALP is located on chromosome 1 and when ALP is mutated it caused HPP. Both males and females are affected equally. 1 in 100,000 live births in Canada are affected by HPP. The Mennonite communities in Canada also have a high amount of births affected by HPP.

Are There Any Prenatal Tests For HPP?

There are not any prenatal tests for HPP because a diagnostic test can only be preformed by looking at the characteristics of the affected areas. It is also common for HPP to be misdiagnosed if the person has a mild case of the genetic disorder.

What Are the Symptoms of HPP?

Within HPP there are five subcategories; perinatal, infantile, childhood, adult, and odontohypophosphatasia. Because cases develop at different rates or are not as threatening, the symptoms can vary between individuals.


The Symptoms Shown in the Perinatal Stage:

  • Bowed arms and legs
  • Underdeveloped ribs
  • Stillbirths
  • Respiratory failure for newborns


The Symptoms Shown in the Infantile Stage:

  • Failure to gain weight
  • Fusion of the bones and skull (craniosynostosis)
  • Skeletal malformations
  • Enlarged wrists and ankle joints
  • Deformed chest and ribs may lead to pneumonia
  • Life-threatening respiratory problems.
  • Bone pain and tender bones
  • In rare occasions seizures may occur


The Symptoms Shown in the Childhood Stage:


  • Skeletal malformations
  • Bone and joint pain
  • Baby teeth fall out earlier than normal
  • Delays in walking


The Symptoms Shown in the Adult Stage:


  • Individuals have osteomalacia
  • Stress fractures
  • Bone pain
  • Pain and inflammation in joints
  • Loss of adult teeth



The Symptoms Shown in Odontohypophosphatasia:


  • Premature loss of teeth
  • Loss of teeth in adult life

Odontohypophosphatasia does not have the characteristics of regular HPP.

Candidacy for HPP

Children with HPP don't have one person to represent them. Because HPP is so rare, the disorder is often recognized with Dr. Whyte's studies and work. All children are given hope through Shriners Children Hospital to be able to walk and play like other children.

How is HPP Inherited?

The severe form of HPP are inherited in an autosomal recessive pattern. In these cases the parents will both carry an altered gene but don't have any signs or symptoms of the disorder.

Mild forms of HPP can have autosomal recessive pattern or the autosomal dominant pattern. Autosomal dominant pattern is the inheritance of an altered gene that is sufficient in the cause of the disorder.

Medical Assistance

Children with HPP are given assistance through safety. Although they are treated through therapy, many cant walk properly or use their arms like a regular child. Shriners Children Hospital cares for many patients with highly dangerous cases of HPP. They regulate the patients intake of food, bowel movements, and activity. They also provide therapy for children with HPP.

Outlooks and Treatments

Infantile cases often need help breathing and surgery to relieve pressure from the skull to help with seizures. Children and Adults have a possibility of looking their teeth. They should see a dentist regularly to preserve their teeth. HPP cases should also cut down on calcium intake because the body produces too much calcium when you have HPP. The rest of the child's life will be affected by HPP. Children with HPP are sent to Shriners and it depends on how severe the case is. If the child has a life-threatening case, they would stay at the hospital to receive treatment. A mild case of HPP will only have to visit Shriners for a week once a year or once every two years. They receive therapy and have to take X-rays but they can be sent home because they are not in serious danger.

Can This Disorder Be Prevented

This disorder is not preventable but can be treated from the point of birth. Cases have shown that their cases have improved with treatment just one day after birth. Enzyme replacement is being tested in mice to further prevent HPP in humans.

Can People With HPP Have Children and Will Their Children Be Affected?

People with mild cases of HPP can have children, but must be cautious of who they decide to have children with because the partner may carry a form of the disorder. Even though both parents have mild cases that they may not know of, the child could be affected much greater and would have a higher chance and having a more severe case of HPP. People with more serious cases of HPP could have problems in their adult life when deciding to have children because their bodies may not be capable and their children could have a much worse case as opposed to a mild cases children.

What is the Current Status of Research On This Disorder?

New information is always being gathered about HPP. Dr. Whyte, the Medical-Scientific Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children, studies children from all over the world with HPP. He is one of the few doctors that is familiar with the rare disorder.

New Treatment

Very recently, new therapy has been approved for HPP. This treatment is only for perinatal, infantile, and childhood cases. Another treatment that was reported recently was treatment from Dr. Whyte and colleagues. This treatment had asfotase alfa and showed improvement in skeletal mineralization and respiratory problem in infantile and childhood patients with life-threatening HPP. Enzyme replacement treatment is also being tested in knockout mice using a bone-targeted recombination to prevent the disease.