Background: Hypophosphatasia (HPP) is a rare, inherited, variable in presentation disorder of bone mineralization, characterized by low alkaline phosphatase (ALP) and elevated blood levels of pyridoxal phosphate (PLP). Enzyme replacement therapy for HPP is available. HPP prevalence remains unknown.
Study design: To diagnose new cases of HPP and ascertain its prevalence in Southern Israel screening of the Clalit Health Services laboratory database serum ALP results over a 14-year period (2002-2016) was performed to identify children with repeatedly low ALP levels (<100 U/L). Family doctors of positive-screened patients were contacted for repeat ALP and PLP levels sampling, followed by radiographs and genetic testing.
Results: Of 658,725 patients analyzed for ALP, 51,032 had one result lower than age and sex adjusted normal values. 2007 patients had > 2 low ALP samples without previously normal levels. 923 were children (< 18 y) and 275 of them had persistent ALP <100 U/L. The first 18 children whose medical records were analyzed include 2 with acute leukemia and 1 with genetically confirmed infantile HPP (who died). In rest 15 patients, 4 had elevated plasma PLP levels and subsequently tested positive for ALPL gene mutations, including: a 4-year old asymptomatic heterozygous girl, a 9 year old boy with nephrolithiasis, a 7 year old girl with dentition problems and late fontanelle closure and her 5 year old brother with chronic leg pain.
Conclusions: HPP is underdiagnosed in Southern Israel. The used diagnostic algorithm may facilitate its early detection and offer life-saving or disease modification by enzyme replacement.
