Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease

Abstract

Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the ALPL gene, resulting in deficient activity of tissue-nonspecific alkaline phosphatase and impaired skeletal mineralization. Affected individuals have a higher prevalence of chronic kidney disease (CKD) than the general population. We report a woman who underwent craniosynostosis surgery in infancy and lost her deciduous teeth prematurely. From age 27, she experienced recurrent foot pain due to multiple metatarsal fractures. Low levels of total alkaline phosphatase (ALP) was noted at 39 years of age, and low activities for the three bone-specific ALP (BALP) isoforms B/I, B1 and B2. Genetic analysis revealed 2 missense variants in the ALPL gene (p.Glu191Lys and p.Gly456Arg) confirming HPP. At age 44, she developed bilateral hip fissures requiring right-sided total hip replacement. Treatment with the parathyroid hormone analogue teriparatide (20 μg/day) was initiated at age 50, leading to increased BALP isoform levels indicating improved mineralization, less bone pain, and no new fractures during 9 months of treatment, which was stopped due to hypercalcemia and hyperphosphatemia. She began peritoneal dialysis at age 55 and received a kidney transplant at age 58. At age 65, seven years post-transplantation, she remained free of new fractures and significant bone pain. This case illustrates the long-term natural history of HPP with progressive skeletal complications across decades, and highlights the potential of short-term teriparatide as a therapeutic option for symptom relief and improved mineralization. It also suggests that kidney transplantation may contribute to improved bone health in HPP with advanced CKD.