MON-753 - Reevaluating the Incidence of Hypophosphatasia in the Era of Enzyme Replacement Therapy: A Retrospective Cohort Analysis

Purpose:
The incidence of hypophosphatasia has been challenging to establish, largely due to several barriers, including its highly variable phenotypic expression, non-specific clinical manifestations, and inherent diagnostic difficulties. The estimated incidence rate of hypophosphatasia is approximately 1 in 100,000 individuals. The primary objectives of this study were: (a) to provide an updated estimate of the incidence rate of hypophosphatasia in the general adult population, and (b) to assess whether serum alkaline phosphatase (ALP) levels could serve as a viable screening tool for identifying individuals who may have hypophosphatasia.

Methods:
Potential subjects were identified through a systematic computerized query of laboratory data within the patient’s electronic medical records (EMR). The search targeted individuals with a serum alkaline phosphatase level less than 40 mg/dL or lower. Subsequently, the medical records of patients who had at least two documented low ALP measurements were subjected to a detailed manual review with the guidance of International Classification of Disease (ICD) codes. Using this approach, individuals with a clinical presentation consistent with hypophosphatasia were identified and included in the analysis.

Results:
A total of 2,688 patients with an ALP less than 40 mg/dL were recognized via a text search from 90,606 patient records. 1,756 patients with a single low ALP level were excluded and not considered for further review. The remaining 932 patients, each of whom had at least two documented low ALP measurements, underwent manual review of their medical histories for findings consistent with hypophosphatasia. Among the 932 patients reviewed, 56 exhibited symptoms and medical histories compatible with hypophosphatasia, including chronic fatigue, muscle weakness, nonspecific chronic pain, reduced mobility, and nonspecific bone disorders. 18 of the 56 patients, less than one-third, had received treatment or genetic testing for hypophosphatasia.

Conclusion:
The results of this study indicate that the incidence rate of hypophosphatasia is likely higher than previously reported. Of the 90,606 patients included in the analysis, 932 were found to have at least two low alkaline phosphatase measurements. Furthermore, within this subgroup, 56 of the 932 patients exhibited symptoms and clinical histories consistent with hypophosphatasia. As a result, the estimated incidence rate of hypophosphatasia may be closer to 1 in 1600 individuals. These findings suggest that systematic identification of patients with persistently low ALP levels represents a reasonable screening strategy for detecting potential cases of hypophosphatasia. This study represents a viable approach to reducing the cost of medical care for patients with potentially a treatable condition that previously may have been missed.

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