Diagnosis and Treatment of Hypophosphatasia (HPP)

Article published Open Source in: Calcified Tissue International (Springer), 2025, 116:46

Authors: Dr. Lothar Seefried, F. Genest, C. Hofmann, M.L. Brandi and E.Rusch

What is this article about: 
Hypophosphatasia (HPP) is a rare genetic disorder caused by variants in the ALPL gene, leading to insufficient activity of tissue-nonspecific alkaline phosphatase (TNAP). It manifests with a range of symptoms including skeletal hypomineralization, rickets, vitamin B6-dependent seizures, and premature loss of teeth. Diagnosis is based on clinical presentations, low alkaline phosphatase activity, elevated ALP substrates, and genetic confirmation. The treatment approach is multimodal and requires a multidisciplinary team to manage metabolic, neurological, and dental care. Asfotase alfa, an enzyme replacement therapy, has shown promising results, but further research is needed to explore its efficacy across various manifestations of HPP. Understanding the complex pathophysiology behind HPP is crucial for improving diagnostic and treatment strategies.

Key Take Aways:
This article will provide valuable insights into:

1. HPP is caused by ALPL gene variants leading to low alkaline phosphatase levels.
2. Symptoms include skeletal deformities, seizures, and early tooth loss.
3. Diagnosis involves clinical evaluation, biochemical tests, and genetic confirmation.
4. Treatment is comprehensive, often requiring a multidisciplinary approach.
5. Asfotase alfa is effective but more research is needed for broader applications.
6. Adult patients exhibit non-classical symptoms, highlighting the need for ongoing management.