Current View on Etiopathogenesis, Clinic, and Diagnosis of Hypophosphatasia in Children: Narrative Review and Case Study Description Represented by Stress Fractures

Hypophosphatasia (HPP) is a monogenic bone disease caused by alkaline phosphatase (ALP) deficiency due to variants in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This disease is systemic due to numerous ALP functions, and it affects musculoskeletal (bone demineralization with rickets-like changes, stress fractures, arthralgias, enthesopathies, early tooth loss), respiratory (pulmonary hypoplasia), nervous (pyridoxine-dependent seizures, chronic pain syndrome), and urinary systems. HPP diagnosis is based on the repeat measurements of ALP activity and its blood and urine metabolites levels, evaluation of X-ray changes, and revealing ALPL gene variants. The only effective treatment for HPP is enzyme replacement therapy with asfotase alfa. This review covers disease mechanisms, its clinical signs, diagnosis and management methods. Unusual case study of HPP with atypical stress fractures is presented.

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