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

Maria Sääf; Sigridur Björnsdottir; Mathias Haarhaus; Ellen Margrethe Hauge; Diana Atanasova; Per Magnusson

doi:10.1016/j.bonr.2025.101872

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

Maria Sääf
, Sigridur Björnsdottir
, Mathias Haarhaus
, Ellen Margrethe Hauge
, Diana Atanasova
, Per Magnusson^*

^*Corresponding author for this work

Department of Clinical Medicine - The Section for Rheumatology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Article number	101872
Journal	Bone Reports
Volume	26
ISSN	2352-1872
DOIs	https://doi.org/10.1016/j.bonr.2025.101872
Publication status	Published - Sept 2025

Keywords

Alkaline phosphatase
Chronic kidney disease
Hypophosphatasia
Teriparatide
Transplantation

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title = "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.",

keywords = "Alkaline phosphatase, Chronic kidney disease, Hypophosphatasia, Teriparatide, Transplantation",

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year = "2025",

month = sep,

doi = "10.1016/j.bonr.2025.101872",

language = "English",

volume = "26",

journal = "Bone Reports",

issn = "2352-1872",

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}

Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease. / Sääf, Maria; Björnsdottir, Sigridur; Haarhaus, Mathias et al.
In: Bone Reports, Vol. 26, 101872, 09.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease

AU - Sääf, Maria

AU - Björnsdottir, Sigridur

AU - Haarhaus, Mathias

AU - Hauge, Ellen Margrethe

AU - Atanasova, Diana

AU - Magnusson, Per

PY - 2025/9

Y1 - 2025/9

N2 - 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.

AB - 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.

KW - Alkaline phosphatase

KW - Chronic kidney disease

KW - Hypophosphatasia

KW - Teriparatide

KW - Transplantation

UR - https://www.scopus.com/pages/publications/105013482034

U2 - 10.1016/j.bonr.2025.101872

DO - 10.1016/j.bonr.2025.101872

M3 - Journal article

C2 - 40894392

AN - SCOPUS:105013482034

SN - 2352-1872

VL - 26

JO - Bone Reports

JF - Bone Reports

M1 - 101872

ER -

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

Abstract

Keywords

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