Suspecting Hypophosphatasia? Symptoms, Diagnosis & What to Do Next

If you or your child are dealing with frequent fractures, bone pain, or early tooth loss, these issues could be signs of a rare disease called hypophosphatasia (HPP). HPP Disease is a genetic disorder that affects bone and tooth strength, with symptoms ranging from mild dental problems to serious bone complications, depending on age.

What is Hypophosphatasia?

Hypophosphatasia is a rare metabolic disorder with a genetic basis, resulting from a congenital metabolic error. A mutation in the ALPL gene causes the loss of function of the tissue-nonspecific alkaline phosphatase (TNSALP). The reduced or absent activity of this enzyme leads to improper mineralization of bones and teeth. This is due to TNSALP’s direct involvement in the mineralization of the skeleton, which cannot proceed normally if the enzyme is not fully or entirely active.

Depending on the age at which the first symptoms appear, several forms of HPP disease are distinguished: perinatal, infantile, childhood, adult, odontohypophosphatasia, and mild prenatal hypophosphatasia.

How Many People Are Affected?

The severe form of this disease occurs with a frequency of 1 in 300,000 births in Europe. The milder form occurs in approximately 1 in 6,000 cases.

Symptoms of Hypophosphatasia

The symptoms depend on the age at which they appear, i.e., the form of the disease.

• Infantile form is associated with rickets (soft, weak bones causing bone pain or bowed legs), which develops in the early months and years of life. 
• Childhood form presents with low bone density, leading to frequent pathological fractures. Additionally, young patients with this disorder struggle with rickets, which negatively impacts their growth and delays walking. Joint pain and swelling may also occur. 
• Adults with hypophosphatasia experience early loss of permanent teeth and frequent fractures of the lower limbs (mainly in the midfoot), which cause pain and weakness. 
• Odontohypophosphatasia is associated with premature eruption of primary teeth and advanced caries. This is one of the mildest forms of HPP disease.

How Is HPP Disease Diagnosed?

An essential part of the diagnosis involves both laboratory tests and molecular genetic testing. A decrease in alkaline phosphatase activity in plasma, along with an increase in phosphoethanolamine (PEA) in the urine is noticeable, although these are not immediate indicators to confirm the presence of hypophosphatasia.

Differential diagnosis is often required to rule out other conditions, such as osteogenesis imperfecta or hypophosphatemic rickets. Low levels of alkaline phosphatase can also result from certain medications (e.g., glucocorticoids, vitamin D toxicity).

It is known that the lower the alkaline phosphatase activity, the more severe the form of the disease. In the perinatal form of the disease, ultrasound examination is also used for diagnosis. X-rays can also confirm the presence of pathological fractures.

Prognosis and Outlook

In cases of adult hypophosphatasia and odontohypophosphatasia (which primarily involve dental issues), there is typically no impact on life expectancy. However, the newborn form and its associated respiratory complications have a high mortality rate (about 50% of children die due to these complications). The perinatal form is the most severe and almost always fatal, usually within a few days to several weeks.

How Can HPP Disease Be Treated?

Infants and children with severe forms of hypophosphatasia (HPP) should receive appropriate medical care to manage symptoms and prevent complications. Treatment approaches may include:

• Early monitoring to detect neurological complications as soon as possible. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen, to relieve pain and reduce painful bone marrow swelling. 
• Surgical treatments using rods or nails (intramedullary fixation) to stabilize frequent fractures. 
• Ankle joint orthoses for children with recurrent stress fractures to provide support and reduce injury risk. 
• Ongoing dental care to manage dental symptoms, support speech development, and improve nutrition. 
• Medication for hypercalciuria (excess calcium in urine), including glucocorticoids and loop diuretics, especially in the infantile form. 
• Asfotase alfa therapy: Since 2015, the EU has approved this enzyme replacement therapy for long-term treatment of childhood-onset HPP. It has shown improvements in joint condition and supported better growth in clinical trials.
  

Living with Hypophosphatasia  – Your Support through Saventic Care

Living with this condition presents unique challenges, but with the right support, individuals can lead active and fulfilling lives. At Savenic Care, we specialize in rare diseases like Hypophosphatasia, offering access to diagnostics and clinical studies. 

Do you suspect you have HPP Disease or another Rare Disease? You can use our free Risk Check for Rare Diseases. Just fill out our Patient Form and we do the rest. Get your secured analysis today, powered by advanced technology and reviewed by our team of medical experts.