Background/Aim: X-linked hypophosphatemia (XLH) is a rare disease caused by inactivating mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, characterized by chronic hypophosphatemia. XLH children present with progressive skeletal deformities (leg bowing, waddling gait, poor growth and disproportional short stature), dental abscesses, and craniosynostosis. Most affected children have been treated so far with multiple daily phosphate supplements and oral active vitamin D analogs. This therapy corrects clinical, biochemical and a radiographic sign of rickets, nonetheless, does not restore stable level of serum phosphate. Scientific evidences support the role of serum phosphate level in fat mass acquisition, i.e. obesity, in the general population. Elevated Body Mass Index (BMI) are recurrently reported in series of adult XLH patients. In addition, XLH patients display chronic hypophosphatemia, despite treatment. Therefore we decided to address the clinical metabolic phenotype, beyond the abnormal skeletal phenotype, in children affected with XLH. The aim of our longitudinal observational study was to investigate the prevalence of obesity and associated factors in a large cohort of children with XLH.
Patients/Methods: We selected 172 XLH-children aged 5-20 years (113 girls / 59 boys). Anthropometric parameters (weight, height, BMI) were collected at birth and during follow-up at mean age of 5.3-8.2-11.3-15.9 years (group 1-2-3-4, respectively). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25-30 or ≥30 kg/m2, respectively).
Results: In each age-group, almost 1/3 of XLH-patients were classified as overweight/obese (29.4% vs 28.7% vs 27.5% vs 36.7% for group 1-2-3-4, respectively). Children without XLH-family history had higher BMI-IOTF at every point of follow-up, compared to those with positive XLH-family history. Moreover, higher BMI-IOTF is significantly associated with treatment duration (23.3±4.4 vs 23.8±3.8 vs 25.2±4.5 kg/m2, for subjects with treatment duration of <5, 5-10 and >10 years, respectively, p for trend=0.025). Multiple regression analysis confirmed that treatment length (β=0.17, 95%CI=0.30-1.73, P=0.005) and absence of XLH-family history (β= -0.13, 95%CI= -0.12 - -2.21, P=0.029) are positively associated with higher BMI-IOTF.
Conclusion: 1/3 of XLH-children have phenotypically unfavourable metabolic profile expressed as increased and progressive overweight/obesity, despite phosphate supplementation. Absence of XLH-family history and length of treatment could be considered clinical factors associated with higher BMI-IOTF in XLH. BMI and metabolic profile should be carefully managed in children, and later adults, with XLH.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology