Hypophosphatasia is a bone mineralization disorder due to deficiency of which enzyme?

• A. Tissue-nonspecific alkaline phosphatase (ALPL).
• B. Phosphatase acid phosphatase.
• C. PHEX enzyme.
• D. Fibroblast growth factor 23 (FGF23)

Answer: (B)

Hypophosphatasia stems from a deficiency of tissue-nonspecific alkaline phosphatase, an enzyme essential for bone mineralization. This enzyme normally hydrolyzes inorganic pyrophosphate (PPi), an inhibitor of mineral deposition. When ALP activity is low, PPi accumulates in the bone matrix and prevents hydroxyapatite formation, so bones and teeth don’t mineralize properly. The result is soft, poorly mineralized bones (rickets in children, osteomalacia in adults) and dental problems such as premature tooth loss. Lab clues often include low alkaline phosphatase activity and elevated substrates like PPi and phosphoethanolamine. The other options involve different pathways: PHEX and FGF23 are part of phosphate handling in X-linked hypophosphatemia, not a deficiency of alkaline phosphatase, and acid phosphatase is not the enzyme deficient in this disorder.