🦴 Chapter 748 · Hyperphosphatasia

🔑 Key Principles — Nelson Chapter 748
• Benign Transient Hyperphosphatasemia (BTH): Most common cause of elevated ALP in children age <5 years. ALP 3,000-6,000 IU/L (isoenzymes bone + liver). Post-viral (including SARS-CoV-2). No clinical symptoms of bone or liver disease. Resolves within 16 weeks. No treatment needed.
• Juvenile Paget Disease (Familial Hyperphosphatasemia, Idiopathic Hyperphosphatasia): TNFRSF11B mutations (osteoprotegerin deficiency) → increased osteoclast activity. Progressive bone deformity (bowing, thickening), fractures, skull enlargement, hearing loss, markedly elevated ALP (often >1,000-2,000 IU/L). Radiographs: cortical thickening, osteopenia, 'cotton-wool' appearance. Treatment: bisphosphonates (pamidronate, zoledronic acid).
• Expansile Skeletal Hyperphosphatasia (ESH): TNFRSF11A mutations (RANK). Similar to juvenile Paget but more expansile lesions. Bisphosphonates.
• Hyperphosphatasia with Intellectual Disability (Mabry syndrome): PIGV, PIGO, PGAP2, PGAP3 mutations (GPI-anchor defects). Elevated ALP, intellectual disability, seizures, distinct facies. No treatment for ALP elevation.
• Differential diagnosis: Physiologic (growth spurts), liver disease (elevated GGT), rickets (high ALP, low Ca/PO4), hyperparathyroidism, osteosarcoma.