Hypophosphatasia results in defective mineralization due to ALPL deficiency; a biochemical hallmark is accumulation of inorganic pyrophosphate. Which statement correctly describes this condition?

• A. Overactivity of alkaline phosphatase increasing mineralization
• B. Excess osteoclast activity causing bone resorption
• C. Vitamin D hypersensitivity causing bone pain
• D. ENZYME deficiency (ALPL) leading to accumulation of inorganic pyrophosphate and defective mineralization

Answer: (D)

Defective mineralization happens because alkaline phosphatase activity is deficient. Alkaline phosphatase normally hydrolyzes inorganic pyrophosphate (PPi) into phosphate, lowering PPi levels that would otherwise inhibit the formation of hydroxyapatite crystals in bone and teeth. When ALPL is deficient, PPi accumulates and blocks mineral deposition, leading to rickets or osteomalacia and dental problems. So describing an enzyme deficiency (ALPL) leading to accumulation of inorganic pyrophosphate and defective mineralization captures the mechanism. The other statements don’t fit because increasing alkaline phosphatase would promote mineralization, osteoclast overactivity is about bone resorption rather than the mineralization defect here, and vitamin D hypersensitivity isn’t the cause of this condition.