What is Hypophosphatasia

Hypophosphatasia (HPP) is a rare, inherited metabolic disorder characterized by defective mineralization of bones and teeth due to low levels of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme deficiency prevents the body from properly processing minerals like calcium and phosphorus, leading to weakened, soft bones and a wide range of systemic complications.

What causes Hypophosphatasia?

Hypophosphatasia is caused by mutations in the ALPL gene, which provides instructions for making the TNSALP enzyme. When this enzyme is inactive or insufficient, inorganic pyrophosphate—a substance that normally inhibits bone mineralization—builds up in the body. This accumulation prevents calcium and phosphorus from depositing into the bone matrix, causing bones to remain soft (osteomalacia) or fail to form properly (rickets). Because the ALPL gene is involved in systemic processes, Hypophosphatasia can affect the entire skeletal system, as well as the teeth and muscles.

What are the different types of Hypophosphatasia?

The severity of Hypophosphatasia varies significantly depending on the age of onset and the nature of the genetic mutation. Clinicians generally classify the condition into these primary forms:

• Perinatal HPP: The most severe form, often detectable before birth; it causes life-threatening complications due to severely underdeveloped lungs and skeleton.


• Infantile HPP: Presents within the first six months of life, often characterized by failure to thrive, respiratory issues, and high calcium levels in the blood.


• Childhood HPP: Varies widely, often presenting with premature loss of primary (baby) teeth, short stature, and skeletal deformities like bowed legs.


• Adult HPP: Typically manifests as recurring stress fractures, chronic bone pain, and early loss of adult teeth.


• Odontohypophosphatasia: A milder form that primarily affects the dental system, resulting in premature tooth loss without significant skeletal abnormalities.

How common is Hypophosphatasia?

Determining the exact prevalence of Hypophosphatasia is challenging because milder forms often go undiagnosed. Current medical literature estimates that severe forms occur in approximately 1 in 100,000 live births. However, when including milder, late-onset forms, some studies suggest a prevalence as high as 1 in 6,000 in certain populations. Currently, 9 individuals living with Hypophosphatasia have joined our DiseaseMaps community, highlighting the importance of connecting with others who share this rare experience.

What differentiates Hypophosphatasia from other bone disorders?

Unlike many other bone conditions, the hallmark of Hypophosphatasia is low serum alkaline phosphatase activity. Many patients with other skeletal disorders have normal or elevated enzyme levels. If you have been diagnosed with "rickets" or "osteomalacia" but your alkaline phosphatase levels are consistently low, it is a strong clinical indicator that Hypophosphatasia should be investigated.

Next steps

• Consult with a metabolic bone specialist or an endocrinologist experienced in rare skeletal disorders.


• Request a genetic test to identify potential ALPL gene mutations.


• Join the Hypophosphatasia community on DiseaseMaps.org to share experiences and learn from others living with the condition.


• Maintain a dental record, as early tooth loss is a unique clinical marker for this disease.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Hypophosphatasia overview.


• Orphanet: Rare disease database entry for Hypophosphatasia (ORPHA417).


• OMIM (Online Mendelian Inheritance in Man): ALPL gene and Hypophosphatasia clinical synopsis (#241500).


• The Hypophosphatasia Foundation: Patient resources and educational materials.