An 18-month-old child has bowed legs, recurrent fractures and premature loss of deciduous teeth. Serum calcium and phosphate are normal, but serum alkaline phosphatase is markedly reduced and urinary pyridoxal-5-phosphate is elevated. Mutations in which gene are responsible?

• A SLC34A3, encoding a renal sodium-phosphate cotransporter
• B PHEX, encoding a phosphate-regulating endopeptidase
• C ALPL, encoding tissue-nonspecific alkaline phosphatase ✓
• D ANKH, encoding a pyrophosphate transport regulator

Explanation

Hypophosphatasia results from ALPL mutations. Loss of tissue-nonspecific alkaline phosphatase allows inorganic pyrophosphate, a natural inhibitor of hydroxyapatite crystallisation, to accumulate and blocks skeletal mineralisation, while pyridoxal-5-phosphate, one of its substrates, piles up in urine. PHEX mutations raise FGF23 and cause X-linked hypophosphataemia with low phosphate and normal or high alkaline phosphatase, which kills option B.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.