Are your bones and teeth weak? Let's learn about this rare condition (Hypophosphatasia)

Have you ever heard of a disease where the bones and teeth become weak and brittle? Maybe you've seen someone in your family or a friend's child have this problem. Today we're going to talk about a rare but very important condition to know about. It's called hypophosphatasia, or HPP.

What is Hypophosphatasia?

Simply put, hypophosphatasia (HPP) is a rare genetic condition. It mainly affects the way your bones and teeth develop. To be precise, this disease causes your bones and teeth to not be as strong or as thick as they should be. In medical terms, they do not mineralize or calcify properly. It falls under the category of metabolic bone disease.

Think about it, our bones are like concrete pillars in a building, they need to be strong. They need the right amount of minerals like calcium and phosphorus. This process doesn't happen properly in the body of someone with HPP. As a result, the bones become soft and weak.

The severity of HPP can vary greatly from person to person. Some people may have it as mild as stress fractures from frequent accidents in middle age. However, in some cases, it can be so severe that the baby can die in the womb (stillbirth) or within a few days of birth.

What are the main types of hypophosphatasia (HPP)?

HPP is divided into seven main types. These are classified according to the age at which symptoms begin and the severity of the disease. Let's take a look at what they are, from most severe to least severe:

• Severe perinatal HPP: This is the most severe type.
• Mild HPP that occurs before birth (perinatal): In this case, some bone development may be seen.
• Infantile HPP: A type that appears after birth.
• Childhood HPP: This can also be mild or severe.
• Adult HPP: Symptoms appear after adulthood.
• Odontohypophosphatasia: This affects only the teeth. Baby teeth fall out quickly.
• Pseudohypophosphatasia: This is very rare. Although the alkaline phosphatase level in the blood is normal, the symptoms are similar to those of infantile HPP.

How common is this disease called HPP?

In fact, HPP is a very rare disease in the general population. Severe cases of HPP affect about one in 100,000 to one in 300,000 babies born each year. However, milder forms of the condition, such as adult HPP, are much less common. That means that about one in 6,000 to 7,000 people may be affected.

The disease is more common among the Mennonite community in Manitoba, Canada, where it is reported that about one in 2,500 babies develop severe HPP.

What are the symptoms of hypophosphatasia (HPP)?

The symptoms of HPP vary widely. Symptoms can vary even within the same family. The symptoms you experience usually depend on the type of HPP you have.

Symptoms of Perinatal HPP

Doctors can often see these features of the fetus during ultrasound scans performed during pregnancy:

• Short, bowed, underdeveloped (under-mineralized) arms and legs.
• Underdeveloped chest ribs.
• Chest deformities (flail chest).

Some pregnancies can end in stillbirth. Some babies may die within a few days of birth from respiratory distress caused by chest weakness.

Symptoms of perinatal benign HPP

Babies with this condition may be born with bowed arms and legs. Doctors can see this during ultrasounds during pregnancy.

However, after birth, these bone deformities gradually improve. Later symptoms can range from infantile HPP to odontohypophosphatasia.

Characteristics of Infantile HPP

Symptoms of infantile HPP usually begin to appear around six months of age. They include:

• Weight gain and growth problems.
• Early loss of baby teeth.
• Abnormal fusion of the skull bones (craniosynostosis), which can cause a change in the shape of the head (brachycephaly).
• Increased pressure inside the skull (intracranial hypertension). This can cause headaches and bulging eyes (proptosis).
• Soft, deformed bones similar to rickets.
• Widening of the bones in the wrist and ankle area.
• Deformities of the chest and ribs and their fractures.
• Difficulty breathing.
• Cases of fever accompanied by bone pain.
• Lack of muscle tone (hypotonia). Some people also call this "floppy infant syndrome".
• Increased calcium levels in the blood (hypercalcemia). This can cause vomiting, constipation, fatigue, and loss of appetite.
• Rarely, seizures may occur.

In some cases, these bone mineralization problems in infantile HPP may improve spontaneously during childhood. However, it is essential to seek treatment to prevent permanent complications (e.g., short stature, bone deformities).

Symptoms of Childhood HPP

Childhood HPP can range from mild to severe. Symptoms may include:

• Age-appropriate bone mineral density loss and spontaneous fractures (this is the main feature of mild HPP).
• Rapid fusion of the skull bones (craniosynostosis) and resulting increased pressure inside the skull (intracranial hypertension).
• Bone deformities that become visible around the age of 2-3.
• Bone and joint pain.
• Premature loss of deciduous teeth. Usually one or more teeth fall out before the age of 5.
• Weakness and delayed walking (not taking the first step by 18 months).
• Waddling gait.

Sometimes, childhood HPP can suddenly improve in young adulthood. However, complications can recur in middle age or old age.

Symptoms of Adult HPP

Symptoms of adult HPP are also very diverse. They include:

• Softening of the bones (osteomalacia).
• Bone pain.
• Loss of permanent teeth (some adults with HPP may have had rickets as children, or may have lost their baby teeth prematurely).
• Fractures, especially stress fractures of the metatarsal bones or pseudofractures (loose zones) of the femur.
• Chronic pain and weakness caused by frequent bone fractures.
• Calcium deposits around the joints, causing joint inflammation (calcific periarthritis) and/or pain.
• Sudden, severe joint pain (chondrocalcinosis or pseudogout, caused by calcium deposits in the cartilage).

Symptoms of Odontohypophosphatasia

This type only affects your teeth - the bones of your skeleton are not affected. The main symptom is that baby teeth fall out prematurely, meaning during infancy or early childhood. Some people may also lose their permanent teeth unexpectedly as they get older.

What causes hypophosphatasia (HPP)?

The main cause of HPP is genetic variants. Specifically, it is caused by mutations in the ALPL gene . Normally, the ALPL gene instructs our body to make an enzyme called Tissue-Nonspecific Alkaline Phosphatase (TNSALP) . This enzyme is essential for our bones and teeth to mineralize properly, meaning they become strong.

Think of this TNSALP enzyme as the chief engineer in a bone-making factory. If it doesn't work properly, the quality of the goods (i.e., bones) that come out of the factory will decrease.

When changes in the ALPL gene prevent the TNSALP enzyme from being produced properly, it cannot do its job properly.

Bone mineralization is the process by which the bone matrix is ​​filled with a solid material such as calcium phosphate. This bone matrix is ​​made up of proteins such as collagen and minerals such as calcium and phosphate.

The most severe forms of HPP are caused by genetic changes that completely block the activity of the TNSALP enzyme. Other genetic changes that reduce the activity of the TNSALP enzyme, but do not completely block it, cause milder forms of the disease.

How is hypophosphatasia (HPP) inherited?

Severe forms of HPP, such as perinatal HPP, are inherited in an autosomal recessive pattern. This means that both parents must pass on the altered ALPL gene to their child. Often, parents do not have symptoms of HPP and are unaware that they carry the gene variation, so the child may be surprised when the disease develops.

Mild forms of HPP can be inherited in either an autosomal recessive or an autosomal dominant pattern. An autosomal dominant pattern means that a child can have the disease even if only one parent inherits the mutated ALPL gene .

How is hypophosphatasia (HPP) diagnosed?

Doctors mainly use physical exams, imaging tests, and laboratory tests to diagnose HPP. A doctor who is familiar with the disease can quickly recognize it. However, a doctor who is not very familiar with HPP may take a while to make a diagnosis.

Tests that help diagnose HPP are:

• Alkaline Phosphatase (ALP) blood test: ALP is an enzyme that is linked to bone mineral density. People with HPP usually have lower ALP levels with age. However, this test alone cannot confirm the disease, as other conditions can also cause low ALP levels.
• Pyridoxal 5ʹ-phosphate (PLP) blood test: PLP is a form of vitamin B6. People with HPP usually have higher levels of PLP.
• X-rays: In severe cases of HPP, X-rays may show bone deformities specific to the disease. However, because there are other causes of bone problems, your child's doctor may not immediately recognize it as HPP.
• Genetic testing: This can identify variations in the ALPL gene that cause HPP. However, this test is not performed in all laboratories.

How is hypophosphatasia (HPP) treated?

There is currently no cure for HPP. However, the main treatment is a vaccine called Asfotase alfa (Strensiq®) . This is a subcutaneous injection, and TNSALP acts as an enzyme replacement therapy. It can be used in children and adults whose symptoms begin in childhood.

Studies have shown that the drug Asfotase alfa can improve breathing, calcium levels, bone health, and survival in children with infantile and juvenile HPP.

Other treatments focus on managing specific symptoms and complications. Your child may need a team of specialists to treat them. These may include:

• Pediatricians
• Orthopedists
• Pediatric endocrinologists
• Pediatric neurosurgeons
• Nephrologists
• Periodontists (specialists in the tissues around the teeth)
• Pain management specialists
• Physical therapists
• Occupational therapists

Some examples of supportive treatments:

• Respiratory support for breathing difficulties.
• Helmet therapy or surgery for craniosynostosis.
• Placing a shunt or cranial surgery to treat increased pressure inside the skull (intracranial hypertension).
• Vitamin B6 for seizures caused by HPP.
• Regular dental care from an early age to assess dental problems.
• Restricting dietary calcium, some diuretics, and calcitonin injections can cause high blood calcium levels (hypercalcemia).
• Nonsteroidal anti-inflammatory drugs (NSAIDs) for bone and joint pain.
• Fractures may require casts, splints, or surgery to fix broken bones (internal fixation).

What should I expect if my child has hypophosphatasia (HPP)?

It's important to remember this: No two people with HPP are affected the same way. No one can predict exactly how your child will develop the condition as they grow up. The best thing you can do is, if possible, talk to a doctor who specializes in researching and treating HPP. They can tell you what symptoms or changes to watch for and what the future holds.

Can hypophosphatasia (HPP) be prevented?

Since HPP is a genetic disease , it cannot be prevented.

If you are concerned about passing hypophosphatasia or other genetic diseases on to your children, talk to your doctor about genetic counseling .

How do I care for my child with HPP?

If your child has HPP, it's important that you get involved to make sure they get the best medical care possible. Some of the doctors you see may not be very knowledgeable about this rare condition. So, by advocating for your child, you can help them get the best quality of life possible.

You and your family may also want to consider joining a support group. This will give you the opportunity to meet others who have gone through similar experiences to yours, talk, and share ideas.

When should my child see a doctor?

If your child has hypophosphatasia, they should meet with their medical team regularly to receive treatment and monitor symptoms.

Understanding your child's HPP diagnosis can be overwhelming. But remember, your child's healthcare team will provide them with a strong management and monitoring plan that is specific to them. It's important to make sure you, your child, and your family get the support they need, and to stay focused on your child's health. Your child's healthcare team is here to support you every step of the way.

What is the take-home message we want to take from this story?

Hypophosphatasia is a rare genetic condition that affects the strength of bones and teeth. The severity of this condition varies from person to person. Early diagnosis and proper management are key.

• Because HPP is a genetic disease , it cannot be prevented.
• Symptoms can begin at any time, from birth to adulthood.
• The most important thing is to recognize the disease quickly and seek treatment from specialist doctors.
• Current treatments (especially asfotase alfa) can control symptoms and improve quality of life.
• If you have any more questions about this, don't be afraid to talk to your doctor. They will help you.

Remember, you are not alone. There are resources and support groups that can help people living with these conditions and their families.

` Hypophosphatasia, HPP, genetic diseases, bone weakness, dental diseases, pediatric diseases, alkaline phosphatase