Abstract
Introduction: Hypophosphatasia (HPP) is an autosomal disease resulting from loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The presentation and severity of the disease is highly variable ranging from perinatal-onset HPP with mortality rates as high as 100%, to adult onset with little mortality but with high disease-burden. Overall estimated prevalence of HPP in the general population is 1:100,000 though it may be significantly higher in specific populations. Hypophosphatasia is a heterogeneous disease that can reveal itself at any age, presenting within a wide range of symptoms. Adult HPP typically presents during middle age and is often misdiagnosed or missed in practice. The objective of this study was to determine the prevalence and burden of hypophosphatasia in an ambulatory care endocrinology practice. Methods: Potential subjects were identified via a computerized text search of the laboratory fields of patient electronic medical records (EMR). Search terms included serum ALP levels of less than or equal to 40 mg/dL. Records of patients with at least two low ALP levels were reviewed manually to identify potential patients with a history consistent with HPP. Results: A total of 315 patients with ALP levels < 40 mg/dL were identified via text search from an estimated 20,000 patient records. Fifty-six patients with a single low level were not considered for further review. The remaining 259 patients were reviewed for histories consistent with hypophosphatasia. These patients were predominantly white (64.9%), with an average age of 55 (+ 15) years, and an average BMI of 28 (+ 7) kg/m(2). Ten of these patients had histories consistent with hypophosphatasia including musculoskeletal pain requiring scheduled use of pain medications, polyarthropathy, chondrocalcinosis, deformity secondary to fractures, low BMD, a history of nontraumatic fracture, delayed or incomplete fracture healing, a history of multiple orthopedic surgeries, fatigue, impaired mobility, impaired gait, impairment of daily activities, a history of renal stones or nephrocalcinosis, and/or high serum B6 levels. None of the identified ten patients were currently being treated or had previously been treated for hypophosphatasia and have subsequently been recommended for genetic testing. Conclusions: Hypophosphatasia is an uncommon condition with a highly variable presentation often resulting in a missed diagnosis. Surveillance of practices by identifying patients with low ALP levels is a reasonable screening approach to identifying potential patients with hypophosphatasia.