12324 Clinical Features And PHEX Variants Of Adults With X-Linked Hypophosphatemia

Abstract Disclosure: L.P. Valadares: None. D.R. Carvalho: None. F.S. Lopes: None. R.S. Oliveira: None. L.G. Castro: None. X-linked hypophosphatemia (XLH), caused by loss-of-function PHEX mutations, is a lifelong renal phosphate-wasting disorder and the main cause of inherited hypophosphatemia. In adults, chronic hypophosphatemia leads to impaired bone mineralization and persistent osteomalacia. Short stature, lower limb deformities and musculoskeletal chronic pain can significantly impact the daily lives of affected individuals. This study aimed to describe the clinical and molecular profiles of 23 adults with genetically proven XLH who are being followed at a tertiary medical center in Brazil. We conducted a retrospective analysis of their medical records. The median age at diagnosis was 3.0 years (IQR 2.0-8.0) and the mean age at first visit at the adult care unit was 30.5 years (±12.7). Their mean final height was 144.2 cm (±10.5), with a mean body mass index (BMI) of 28.1 kg/m2 (±4.9). Nine patients were overweight, and seven were obese. Sixteen patients had a positive family history of rickets, and nine had offspring with XLH. Among the 14 different PHEX mutations that were identified, six had not been previously reported. Hypophosphatemia was observed in 21 patients at presentation at the adult care unit, increased serum alkaline phosphatase levels in 19, and 12 showed increased PTH levels. Chronic bone and muscular pain were reported by sixteen patients, eighteen had lower limb deformities, and six had a history of fractures and/or pseudofractures. Seventeen patients underwent orthopedic surgeries, with an average of 3.8 surgical interventions per patient. Nephrolithiasis and/or nephrocalcinosis were observed in nine patients, but none had glomerular filtration rate below 60 mL/min adjusted to 1.73 m2 of body surface. Three patients were on conventional treatment (phosphate and calcitriol) upon presentation at the adult care unit, five patients had never received XLH-specific treatment, and fifteen discontinued conventional therapy after completing skeletal growth, with a mean therapy duration of 12.1 years (±3.5). Out of the 20 patients without treatment, 16 were initiated on pharmacological therapy based on symptoms and signs of persistent osteomalacia. Eleven started combined phosphate and calcitriol supplementation, while five received calcitriol monotherapy. This cohort underscores that adults with XLH experience significant musculoskeletal morbidity throughout their lives, and require long-term follow-up, including assessment of energy metabolism. Importantly, most of them benefits from maintaining pharmacological treatment in adulthood. Presentation: 6/2/2024