# Delayed diagnosis of X-linked hypophosphatemia in the absence of family history: a global unmet need

## TL;DR

Children without a family history of X-linked hypophosphatemia are diagnosed later than those with a family history, highlighting a need for better awareness among healthcare providers.

## Contribution

This study reveals a significant delay in diagnosing XLH in children without a family history, emphasizing the need for improved recognition of early symptoms.

## Key findings

- Children with a family history of XLH are diagnosed at a younger age compared to those without.
- Diagnosis delays persist even in families known to be affected, suggesting broader awareness issues.
- Real-world data from two registries confirm the diagnostic delay in XLH without family history.

## Abstract

X-linked hypophosphatemia (XLH) is a phosphate-wasting disorder mediated by increased fibroblast growth factor 23 (FGF23) activity. Typical clinical features are skeletal deformities, muscle weakness, stiffness, and impaired physical function. Using real-world data from the XLH Disease Monitoring Program (XLH-DMP) and the International XLH Registry, this study sought to determine whether the age at which XLH is diagnosed differs between children with and without a family history of the disease. In both real-world studies, children with a family history of XLH were diagnosed at a younger age than those without a family history (XLH-DMP [n = 347]: mean age at diagnosis 1.6 [standard error (SE) 0.2] vs 2.7 [SE 0.2] years [p < .001]; International XLH Registry [n = 360]: mean age at diagnosis 1.8 [SE 0.2] vs 4.1 [SE 0.3] years [p < .001]). After controlling for sex, race, ethnicity, and country of residence (Cox proportional hazards model), children with a family history of XLH received a diagnosis of XLH at a younger age than those without a family history (XLH-DMP: hazard ratio 1.69, 95% confidence interval [CI] 1.33-2.16; International XLH Registry: hazard ratio 2.47, 95% CI 1.88-3.24). This study demonstrates that children without a family history of XLH are diagnosed at a significantly older age than those from families known to be affected, and that diagnosis may also be delayed despite a family history of XLH. A greater awareness of XLH and its early symptoms among pediatric healthcare professionals is required to avoid delays in diagnosis and treatment initiation.

Graphical Abstract