Clinical and molecular profiles of 14 new patients with X-linked hypophosphatemia (XLH) in greece

Anna Papadopoulou; Symeon Tournis; Elpis Vlachopapadopoulou; Athanasios Siolos; Maria Yavropoulou; Artemis Doulgeraki; Ioanna Paspati; Hionia Haralambidou; Paraskevi Moutsatsou

doi:10.1530/endoabs.110.EP186

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Endocrine Abstracts (2025) 110 EP186 | DOI: 10.1530/endoabs.110.EP186

ECEESPE2025 ePoster Presentations Bone and Mineral Metabolism (142 abstracts)

Clinical and molecular profiles of 14 new patients with X-linked hypophosphatemia (XLH) in greece

Anna Papadopoulou ¹ , Symeon Tournis ² , Elpis Vlachopapadopoulou ³ , Athanasios Siolos ⁴ , Maria Yavropoulou ⁵ , Artemis Doulgeraki ⁶ , Ioanna Paspati ⁷ , Hionia Haralambidou ⁸ & Paraskevi Moutsatsou ⁹

Author affiliations

¹University General Hospital "Attikon" & Saint Sophia Children’s Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece; ²KAT Hospital, National & Kapodistrian University of Athens, Athens, Greece, Laboratory for Research of the Musculoskeletal System “Th. Garofalidis”, Athens, Greece; ³Children’s Hospital P. A. Kyriakou, Endocrinology-Growth and Development, Athens, Greece; ⁴Department of Endocrinology, Ioannina University Hospital, Endocrinology, Ioannina, Greece; ⁵LAIKO General Hospital of Athens, National and Kapodistrian University of Athens, First Department of Propaedeutic and Internal Medicine, Endocrinology Unit, Athens, Greece; ⁶Institute of Child Health, Department of Bone and Mineral Metabolism, Athens, Greece; ⁷Pentelis General Children Hospital, Athens, Greece; ⁸Ippokrateio General Hospital, Thessaloniki, Greece; ⁹University General Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Laboratory of Clinical Biochemistry, Athens, Greece

JOINT1792

Background: X-linked hypophosphataemia (XLH;#307800), is a rare metabolic disorder and the most common form of hereditary hypophosphatemic rickets. Patients present with renal phosphate waste resulting in hypophosphataemia, rickets and osteomalacia due to elevated serum FGF23. The disease is caused by inactivating variants throughout the PHEX gene (*300550) which encodes a 749 amino acid transmembrane protein. These variants are predicted to cause loss of protein function, with the majority producing a truncated protein, while controversy exists regarding genotype-phenotype correlation. In the present study, we performed the genetic analysis of 14 new patients with clinical features of hypophosphatemic rickets, in the frame of definitive diagnosis and selection of treatment.

Materials and Methods: All 22 exons and their flunking intronic regions of the PHEX gene were analysed using direct sequencing. The detailed clinical features of the patients were recorded and genotype-phenotype correlations were performed.

Results: We found 10 different pathogenic genetic variants in 13 different patients, including frameshift, splicing, missense and nonsense changes in the PHEX gene, affecting the extracellular sequence of the protein. Two of the observed genetic variants have not been previously reported (c.2051_2061dup; c.1525A>C). One patient did not reveal any pathogenic variant either by sequencing or MLPA. All patients presented with disproportionate short stature and bowing of the legs; 4/14 osteoarthritis, 8/14 bone pain, 5/14 fractures, hypophosphatemia, and normal to high serum PTH and ALP. Patients carriers of truncated mutations experience more severe phenotypes than patients with missense mutations.

Conclusions: This is the first study describing the detailed molecular and clinical profiles of X-linked hypophosphatemic patients in Greece. Most of them have, recently, started receiving burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23, and their response to treatment is being recorded.