Which metabolic bone disorder is associated with accumulation of inorganic pyrophosphate due to ALPL enzyme deficiency?

Which metabolic bone disorder is associated with accumulation of inorganic pyrophosphate due to ALPL enzyme deficiency?

• A. Hypophosphatasia (ALPL deficiency)
• B. Osteogenesis imperfecta
• C. Osteoporosis due to estrogen deficiency
• D. Hyperparathyroid bone disease

Answer: (A)

Defective mineralization from lack of ALPL activity is being tested. ALPL encodes tissue-nonspecific alkaline phosphatase, which normally hydrolyzes inorganic pyrophosphate (PPi) to phosphate. PPi is a natural inhibitor of hydroxyapatite formation, so when ALPL is deficient, PPi accumulates and mineralization of bone and teeth is impaired. This leads to hypophosphatasia, characterized by low alkaline phosphatase levels and poorly mineralized bone, with features like rickets-like changes in children or osteomalacia in adults and sometimes premature loss of teeth. Osteogenesis imperfecta is caused by defects in collagen type I, not PPi accumulation. Osteoporosis from estrogen deficiency involves reduced bone mass, not a mineralization blockade from PPi. Hyperparathyroid bone disease reflects increased bone turnover and resorption due to excess parathyroid hormone, rather than ALPL-related PPi buildup.

Defective mineralization from lack of ALPL activity is being tested. ALPL encodes tissue-nonspecific alkaline phosphatase, which normally hydrolyzes inorganic pyrophosphate (PPi) to phosphate. PPi is a natural inhibitor of hydroxyapatite formation, so when ALPL is deficient, PPi accumulates and mineralization of bone and teeth is impaired. This leads to hypophosphatasia, characterized by low alkaline phosphatase levels and poorly mineralized bone, with features like rickets-like changes in children or osteomalacia in adults and sometimes premature loss of teeth.

Osteogenesis imperfecta is caused by defects in collagen type I, not PPi accumulation. Osteoporosis from estrogen deficiency involves reduced bone mass, not a mineralization blockade from PPi. Hyperparathyroid bone disease reflects increased bone turnover and resorption due to excess parathyroid hormone, rather than ALPL-related PPi buildup.