Hypophosphatasia (HPP) presents a significant diagnostic challenge, particularly in adults. This rare, inherited metabolic disorder stems from a deficiency in the tissue non-specific alkaline phosphatase (TNSALP) enzyme, a consequence of pathogenic variants within the ALPL gene. The implications of this enzyme deficiency are wide-ranging, leading to diverse clinical manifestations across the lifespan. While severe and even lethal forms of HPP are recognized in newborns and infants, and milder presentations are observed in childhood, diagnosing HPP in adults is often more complex. The signs and symptoms in adults can be subtle and easily mistaken for other conditions, contributing to underdiagnosis or misdiagnosis, especially among clinicians less familiar with this rare disease. Delayed or missed diagnosis can hinder appropriate management and negatively impact patient outcomes.
The absence of established diagnostic guidelines specifically for adults with HPP further complicates the diagnostic process and contributes to inconsistencies in identification. To address this critical gap, the HPP International Working Group undertook a comprehensive review of existing literature. By analyzing 119 relevant research papers focusing on Hpp Diagnosis in adults, sourced from Medline, Medline In-Process, and Embase databases using the search terms “hypophosphatasia” and “HPP,” the Working Group aimed to identify robust diagnostic criteria. Their analysis involved evaluating the prevalence of 17 potential diagnostic characteristics, initially identified by HPP clinical experts, across the collected studies and patient data.
This rigorous evaluation process led to the identification of six diagnostic findings with a pooled prevalence exceeding 50%. These findings were then carefully considered as potential major diagnostic criteria. Through extensive discussion and deliberation among the members of the Working Group, a consensus was reached, resulting in the definition of four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. The Working Group proposed a practical diagnostic approach for adults, emphasizing the integrated application of these criteria. Specifically, they suggested that a diagnosis of HPP in adults could be established by the presence of either two major criteria, or a combination of one major criterion and two minor criteria. This framework represents a significant step forward in improving the accuracy and consistency of HPP diagnosis in the adult population, ultimately aiming to facilitate timely and effective management for individuals affected by this challenging condition.
