Hypophosphatasia is a rare metabolic bone disease characterized by impaired activity of the tissue-nonspecific alkaline phosphatase caused by the mutation of the ALPL gene. The varied clinical manifestations of hypophosphatasia may affect several organs and systems (skeleton, muscle, dental and neurological). Presentation of the disease may range from a lethal perinatal phenotype to the pediatric and adult disease.
In adults, the diagnosis of hypophosphatasia may be delayed by low specificity of clinical manifestations and hetereogeneity of symptoms. Additionally, as Desborough et al. pointed out in a recent article, the low awareness of the disease may lead to misdiagnosis and/or late diagnosis. The authors reported interesting data on the clinical and biochemical characteristics of 20 adult patients with hypophosphatasia.
They observed a higher prevalence of foot and femoral shaft fractures and lower of vertebral fractures in patients with hypophosphatasia compared with a control group of 21 adult patients with low BMD. Additionally, ALP and pyridoxal 5′-phosphate levels were 3-fold lower and 7-fold higher, respectively, while bone resorption markers were higher in patients with hypophosphatasia vs the control group. Interestingly, Desborough et al. identified a threshold of 43 IU/L or less of total alkaline phosphatase as useful, in association with clinical findings, for the differential diagnosis of hypophosphatasia vs osteoporosis. Evaluation of other biomarkers, such as P1NP, osteocalcin, PTH, calcium and phosphate, did not show any betwen-group difference. Similar findings were detected as far as assessment of physical function.
Authors suggest that the association of clinical features, particularly the history of lower extremities fractures, and serum biomarkers, such as total ALP and pyridoxal 5′-phosphate levels, are important tools for an accurate diagnosis of hypophosphatasia and to distinguish the disease from other metabolic bone disorders.
The interesting results of this study draw attention on a rare metabolic bone disease for which an accurate algorithm reporting diagnostic criteria to be employed in clinical practice is currently not available. Such diagnostic tools would help in orientating clinicians on a disease whose diagnosis, although rare, will significantly change patient’s management. This is particularly important in consideration of the reported high delay of diagnosis of hypophosphatasia in adult patients, in which clinical manifestations are frequently just present during the childhood, but unrecognized. Further prospective and larger clinical studies will help in identifying specific and accurate diagnostic criteria whose usefullnes will be of high value in clinical practice.