FROM GENES TO CARE: ADVANCING CLINICAL UNDERSTANDING OF HYPOPHOSPHATASIA

From genes to care, the story of hypophosphatasia reminds us that progress in medicine isn't only about scientific discovery, it's about turning knowledge into healing.

- By Dr Srinivas Kandula, Senior Endocrinologist, CARE Hospitals, Musheerabad, Hyderabad

Bringing a Rare Condition into the Spotlight

Every so often, a rare disorder teaches us something profound about human biology and the impact of how personalised medicine can change lives. Hypophosphatasia, often abbreviated as HPP is one such example. Though few people have heard of it, its story bridges genetics, biochemistry, and compassionate care.

For decades, this condition puzzled doctors. Babies were born with bones so soft that they couldn't support breathing. Adults suffered repeated stress fractures that never healed properly. Some patients lost teeth early in life for no obvious reason. All shared one hidden trait unusually low levels of an enzyme called alkaline phosphatase.

We now know that hypophosphatasia is an uncommon genetic disorder that can range from minor oral issues to potentially fatal skeletal disease, making it more than just a medical curiosity. Additionally, there are now therapeutic possibilities that were previously unthinkable because of current science.

The Role of a Single Gene

The underlying cause of hypophosphatasia is a defect in a single gene, ALPL. It carries the instructions for an enzyme called tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme plays a quiet but essential role in helping our bones and teeth form properly. It acts like a molecular “cleanup crew,” clearing away substances that would otherwise interfere with bone mineralisation.

When mutations occur in the ALPL gene, the body produces too little of this enzyme, or it doesn't work correctly. One of the substances that builds up as a result is inorganic pyrophosphate, a natural inhibitor of bone formation. The higher its concentration, the harder it becomes for calcium and phosphate to bond and form strong bones and teeth.