Inadequate pediatric reference ranges impede the diagnosis of X-linked hypophosphatemia and hypophosphatasia in Austria.

Background: Accurate diagnosis of many pediatric disorders relies on age-specific laboratory reference ranges. This is particularly important for rare disorders such as X‑linked hypophosphatemia (XLH) and hypophosphatasia (HPP), which present with decreases in serum phosphate and alkaline phosphatase (ALP), respectively.

Objective: This study evaluated the use of pediatric reference ranges among Austrian medical laboratories.

Methods: A comprehensive list of all extramural clinical laboratories was compiled. A standardized serum sample with pathological values for a 4-year-old child was dispatched to 26 extramural laboratories. The returned absolute and stated reference values were assessed and analyzed.

Results: Of 22 responding laboratories, 18.2% used appropriate pediatric reference ranges for serum phosphate and 40.9% for ALP. In total, 54.5 and 36.4% of laboratories identified the sample as normal for serum phosphate or ALP, respectively.

Conclusion: Despite accurate absolute value measurements, the majority of laboratories failed to identify the test sample as pathologic. In a real-world setting, the results obtained could lead to significant diagnostic delays and missed diagnoses in pediatric patients. The lack of regulatory requirements for pediatric-specific reference ranges in Austria and most European countries contributes to this problem. The study highlights the need for standardization and mandatory implementation of pediatric reference ranges to improve diagnostic accuracy for rare pediatric disorders across Europe.