ESPE Abstracts

X-linked hypophosphataemia (XLH) is a dominant disorder caused by mutations in PHEX (located at Xp22.1), associated with rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children. The characteristics and severity of XLH vary between patients. Early diagnosis and specific treatment is usually decisive to improve short and long term patient outcomes. We describe the variability of phenotype in two sisters carrying the same PHEX genotype and similar therapeutic history. Anita starts walking at 12 months. She subsequently presents a progressive severe varus lower limbs. In the family history the mother has had a surgically corrected varus lower limbs with good response but residual bone and joint pain. The laboratory exams lead to the diagnosis of hypophosphatemic hyperphosphaturic rickets both in doughter and mother suspecting an X-linked trasmission (XLH). At the age of two, Anita initiate appropriate oral medical therapy with calcitriol and phosphate. The genetic analysis don’t find the classic mutation of the PHEX gene, but a deletion of exon 1 and 2 of the gene, also present in the mother. When the girl is two years old, her sister Giulia is born. She comes to endocrinological attention at 12 months without signs of rickets, the screening blood test show an hyperphosphaturic hypophosphataemia and specific oral medical therapy is immediately started. During her growth, the eldest daughter Anita presents a worsening varus lower limbs, that needs numerous orthopedic surgeries with partial benefit. Giulia, instead, presents only a slight varus corrected with physiotherapy. In 2019, Giulia satisfies the clinical and radiological criteria and starts monoclonal therapy with Burosumab with adequate biochemical response but poor response in height growth due to little residual growth plates. Anita shows, at the time, the fusion of the growth plates and continues oral medical therapy. Anita reaches a definitive height of 148 cm, with an important disproportion due to a still important varus that has poorly responded also to orthopedic interventions. Giulia a height of 153 cm, both below the parental target, despite the small difference in the beginning of the therapy. Our family case underlines the high variability of XLH genotype-phenotype correlation, considering the mother and two sister therapeutic and clinical history. Moreover, our case report highlights the importance of a careful family history in the early diagnosis of genetic diseases which allows for earlier therapeutic intervention and a better clinical prognosis.