Endocrine Abstracts

JOINT2030

Background and Aim: X-linked hypophosphatemia (XLH) is a rare genetic disease hallmarked by hypophosphatemia and osteomalacia with skeletal deformities, caused by autonomous over-secretion of fibroblast growth factor 23 (FGF-23). Obesity is frequently observed in XLH patients, attributed to impaired mobility, but possibly also linked to direct negative metabolic effects of elevated circulating FGF23. Recent research suggests that adult XLH patients are obese with excess fat mass, but without increased prevalence of metabolic dysfunction.

Patients and Methods: Cross-sectional pilot study included a single-centre cohort of 9 adult XLH patients (8 female), 39.9 ± 4.6 years old, treated with active vitamin D and phosphate supplements. Anthropometric analysis included weight, height, BMI, and waist to hip circumference ratio (WHR). Body composition was analysed by DXA whole body scan - WBS (Hologic Discovery QDR). Total body fat percent (Fat%) was expressed as fraction of the upper limit of normal age and gender values (Fat%ULN). Fasting blood glucose and fasting insulin were used to calculate HOMA IR. Abdominal ultrasound was performed to screen for liver steatosis.

Results: The average body weight (60.33 ± 3.45kg) and BMI (29.24 ± 1.81 kg/m²) were on the borderline of overweight and obesity. Four patients were obese (44.4%) and 3 (33.3%) overweight. Average WHR (0.79 ± 0.02) was below the threshold for abdominal obesity. DXA WBS revealed the average total body fat mass (FM) of 23.46 ± 2.6kg, the average total lean body mass (LMB) of 35.75 ± 1.93kg. The average Fat% of 37.73 ± 2.68%, translated to 0.89 ±0.05 Fat%ULN. The average baseline insulin level was 16.30 ± 2.82 mIU/land the average HOMA IR was 3.56 ± 0.56. Seven patients (77.8%) had HOMA IR > 2.4. Abdominal ultrasound revealed liver steatosis in 1 of 9 patients (11.1%).

Conclusions: Adult XLH patients in our pilot single centre cohort were predominantly overweight and obese but with average total body fat percent not exceeding upper limit of age and sex normal values and with average waist to hip ratio indicating low metabolic risk. Prevalence of liver steatosis upon sonography was low. However, average insulin resistance was higher than previously reported, possibly linked to factors beyond the obesity or body composition. Further research may elucidate correlation of insulin resistance with circulating FGF23 and the effects of anti-FGF23 antibody treatment on metabolic status in XLH patients.