1 - Unidade de Nefrologia, Área da Pediatria, Centro Hospitalar Universitário de Lisboa Central, E.P.E.
2 - Unidade de Endocrinologia, Área da Pediatria, Centro Hospitalar Universitário de Lisboa Central, E.P.E.
- 53th Annual Scientific Meeting of the European Society for Paediatric Nephrology, Amsterdão, 16/19/9/2022, Poster
- Pediatric Nephrology (2021) 36:3471.
Abstract:
Objectives: X-linked hypophosphatemia (XLH), a disorder caused by mutations in PHEX, impairs the inactivation of FGF-23 resulting in renal wasting of phosphorus, hypophosphatemia and rickets. Early diagnosis and treatment are important to prevent subsequent sequelae. We report a severe case of XLH due to a novel PHEX mutation. Our aim is to raise awareness about this disease and the potential factors contributing to its severity.
Methods: Clinical case description.
Results: A five-year-old girl from Guinea-Bissau was referred to our tertiary hospital for evaluation of progressive limb deformities since the age of two. Physical examination showed enamel defects, absent superior incisive teeth, genu valgum, severe tibial curvature in the sagittal plane, widening of metaphyseal ends and height-for-age index below -3 z-score. Laboratory workup revealed elevated alkaline phosphatase (1251 U/L), hypophosphatemia (2.8 mg/dL), borderline low serum calcium levels (total calcium 9.1 mg/dL; Ca++ 1.08 mmol/L); low 25-hydroxyvitamin-D (18 ng/mL), high 1,25-dihydroxycholecalciferol (124.18 pg/mL) and PTH (231.7 pg/mL); tubular reabsorption of phosphate (57%) and TmP/GFR (2.22 mg/dL) were low. The x-rays showed metaphyseal widening, diaphyseal trabeculation, rarefaction and pseudofractures. The patient was started on phosphate and calcium supplementation, alfacalcidol, and cholecalciferol. Additionally, she underwent orthopedic surgery twice resulting in partial improvement of the genu valgum. At the age of eight, a novel heterozygous PHEX mutation (c.156_174del) was identified. She started receiving treatment with burosumab, showing clinical improvement.
Conclusions: The patient was referred to us only three years after the identification of bone deformities, which led to a significant delay in the genetic diagnosis and appropriate treatment initiation. The coexisting vitamin D deficiency may have also contributed to the severity of the disease presentation. Additionally, we question whether the truncate mutation may have played a role in this case severity. Considerable controversy exists regarding the correlation between truncating mutations and a more severe phenotype in XLH.
Keywords: burosumab, X-linked hypophophataemia