Hypophosphatasia, which exhibits both autosomal dominant and recessive inheritance, results from tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) deficiency caused by 𝘈𝘓𝘗𝘓 alterations. TNSALP deficiency leads to accumulation of pyridoxal 5′-phosphate (the main circulating form of vitamin B6), phosphoethanolamine, and inorganic pyrophosphate. Elevated levels of inorganic pyrophosphate, together with locally reduced levels of inorganic phosphate, inhibit hydroxyapatite formation and impair skeletal and dental mineralization (seen in image).

Learn more and read about a clinical case involving this disorder in the Clinical Problem-Solving feature “Break a Leg” by M. Wijnen et al.: https://nej.md/4zOIkwu