Hypophosphatasia – Prenatal onset

What else is it called?

Prenatal benign hypophosphatasia is also known as: 

  • Prenatal benign rathburn disease 
  • Prenatal benign phosphoethanolaminuria 
  • PB-HPP 

Perinatal lethal hypophosphatasia is also known as: 

  • Perinatal lethal rathburn disease 
  • Perinatal lethal phosphoethanolaminuria  
  • PL-HPP 

Get in touch

Contact our caring team on 08452 412 173 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Prefer to email? Our email address is contact@metabolicsupportuk.org.

What causes it?

Prenatal lethal hypophosphatasia:

PL-HPP is caused by mutations in the gene called tissue nonspecific alkaline phosphatase (TNSALP) which provides instructions for the protein known as tissue nonspecific alkaline phosphatase. By having a problem in the TNSALP gene it will cause the protein to be made incorrectly which causes poor development and health of the bones and teeth and the accumulation of certain chemicals in the body. 

Prenatal benign hypophosphatasia:

PB-HPP is caused a problem in the ALPL gene, the ALPL genes provides instructions for a specific protein known as tissue non-specific alkaline phosphatase. By having a problem means that the body will be unable to use calcium for bone calcification which means that bones will be fragile. 

How common is it?

The true incidence of PL-HPP is unknown because of how rare HPP as a whole is. However, in Europe the prevalence of perinatal hypophosphatasia is estimated to be 1:530,00 which was based on molecular diagnosis made from 2000 to 2009. However, there are specific regions in the world in which the prevalence of HPP is much higher, these regions are: the Mennonite community in Canada and an endogamous village in Hungary. PL-HPP is more common in Caucasian communities and it is rarer in black communities. 

The true incidence of PB-HPP is unknown due to the rarity of hypophosphatasia.

What are the signs and symptoms?

Prenatal lethal hypophosphatasia:

PL-HPP begins to manifest while a baby is in the uterus. The signs and symptoms are:  

  • Skeletal malformations 
  • Short bowed arms and legs 
  • Under-developed ribs 

This inherited disorder has a high mortality rate with some pregnancies ending in a still birth. In some occasions the baby is born and survives a few days but passes away due to respiratory failure caused by the chest deformations and under-developed lungs. 

Prenatal benign hypophosphatasia:

PB-HPP begins to manifest during the first six months of life, since it’s the benign (less severe) form of HPP it later resolves into what looks like childhood hypophosphatasia. The signs and symptoms of PB-HPP are: 

  • Skeletal malformations 
  • Bowed limbs 

How is it diagnosed?

Prenatal lethal hypophosphatasia:

PL-HPP can be diagnosed using molecular genetic testing which can detect problems in the ALPL gene. PL-HPP can also be diagnosed using sonographic and radiographic medical tools which are used to examine if there is any structural anomalies. 

Prenatal benign hypophosphatasia:

PB-HPP is diagnosed via ultrasound to detect any deformations during the third trimester of the pregnancy. The prognosis is generally good as the skeletal deformations associated with PB-HPP eventually resolve themselves and patients develop manifestations which are similar to Childhood-HPP. 

 

Can it be treated?

Prenatal lethal hypophosphatasia:

There is limited treatment for PL-HPP with enzyme replacement therapy. There are also expectant management and family support options available. 

Prenatal benign hypophosphatasia:

PB-HPP can be managed using a specific diet which includes staying away from vitamin and mineral supplements.  

Do my family need to be tested?

PL-HPP and PB-HPP are an autosomal recessive inherited disorder. Humans are made up of DNA and the DNA is made up of chromosomes. Genes are sections of DNA which provide instructions to produce a protein that has a specific function. When there is an issue with a particular gene it causes the protein to be made incorrectly leading to disease. Humans inherit chromosomes from both their mother and father in the forms of eggs and sperm and these chromosomes determine the child’s characteristics. An inherited autosomal recessive disease is a disease that a child will inherit from their parents. Every human has two genes needed to make a functioning TNSALP and when both of the genes are not working PL-HPP or PB-HPP will develop. For a child to develop PL-HPP or PB-HPP they will need to inherit one non-working gene from each parent. The parents do not necessarily need to be diagnosed with PB-HPP to pass it on, they can also be carriers. a carrier is someone who possess’ one non-working gene but does not have the disease because the other gene is working correctly.  

In the event that both of the parents are carriers of PL-HPP or PB-HPP. There is a: 

  • 25% chance that one of the children will be unaffected by PL-HPP or PB-HPP and will not be a carrier. 
  • 25% chance that the child will inherit PL-HPP or PB-HPP. 
  • 50% chance that the child will be unaffected by PL-HPP or PB-HPP and will be a carrier. 

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002]. 

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