Introduction: Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive condition caused by inactivating mutations in the GALNT3 gene, characterised by elevated serum phosphate and 1,25(OH)2 vitamin D, increased urinary tubular reabsorption of phosphate and hyperostosis of long bones.
Case report: A 15-year-old boy (weight +1.05 SD; height −0.1 SD) with consanguineous parents of Palestinian descent, presented with a 6 year history of recurrent episodes of flitting pain in his forearms and lower legs. Episodes typically lasted 14 weeks were associated with erythema of the overlying skin, swelling of the underlying tissue with no obvious triggers. Previous investigations had included a biopsy of the ulna which revealed only non-specific findings (ossified material surrounding calcified cartilaginous tissue). Diagnoses of osteopetrosis and chronic recurrent multifocal osteomyelitis (CRMO) had been made in the past. Treatment with intermittent glucocorticoids and NSAIDS had produced symptomatic benefit. General examination was unremarkable apart from thickening and widening of the right ulnar border and anterior border of the right tibia. Biochemical investigations showed a persistent high fasting serum phosphate (2.29 mmol/l) with an inappropriately elevated TmP/GFR (3.11 mmol/l). Serum 25(OH) vitamin D concentration was low (13 nmol/l), 1,25(OH)2 vitamin D was elevated (195 pmol/l) and PTH was previously normal (6 pmol/l). Radiographs showed mild periosteal reaction, cortical irregularity and poor cortico-medullary distinction throughout the shafts of the radius, ulna, tibia and fibula. MRI revealed high signal lesions within the medullary cavity of the diaphyses of the left fibula and right tibia on T2-weighted and STIR, corresponding to low signal on T1 sequences. Mutation analysis of the GALNT3 gene revealed a homozygous GALNT3 frame shift mutation (c.803dupC), confirming the clinical diagnosis of HHS.
Conclusion: This case illustrates the value of both thorough clinical assessment and targeted genetic screening in the prompt diagnosis of rare disorders. This case illustrates the value of both thorough clinical assessment and targeted genetic screening in the prompt diagnosis of rare disorders.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology