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23.06.2023 | Original Article

Musculoskeletal pain and muscular weakness as the main symptoms of adult hypophosphatasia in a Spanish cohort: clinical characterization and identification of a new ALPL gene variant

verfasst von: Pilar Calmarza, Carlos Lapresta, María Martínez García, José Ochoa, Paula Sienes Bailo, Javier Acha Pérez, Jesús Beltrán Audera, Eva González-Roca

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 5/2023

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Abstract

Introduction

Hypophosphatasia (HPP) is a rare inherited disorder, caused by mutations in the alkaline phosphatase (ALPL) gene, which encodes for the tissue non-specific alkaline phosphatase (TNSALP) isoform of alkaline phosphatase (ALP). Adult HPP is one of the mild forms that presents with unspecific signs such as osteopenia, osteomalacia and muscle involvement. Our purpose was to identify and characterize possibly misdiagnosed adult HPP patients at a clinical and biochemical level.

Material and Methods

At the laboratory of Miguel Servet University Hospital we retrospectively reviewed serum ALP levels in adults over a 48-month period. The clinical records of individuals with consistently low ALP levels were reviewed to exclude secondary causes. Those with persistent hypophosphatasemia were screened for symptoms of HPP. The study participants were evaluated at biochemical and genetic levels.

Results

We identified 705 ALP determinations (out of 384,000 processed) in 589 patients below the reference range (30 U/l). Only 21 patients with clinical signs and symptoms of HPP were selected for genetic testing. Finally, only 12 patients participated in the study, 83.3% of whom (10/12) harbored a pathogenic or likely pathogenic variant in a heterozygous state. The major symptoms of our cohort were the presence of musculoskeletal pain (100% of patients) and muscular weakness (83.3% patients).

Conclusion

Mild HPP patients presenting with diffuse symptoms such as musculoskeletal pain may be undiagnosed or misdiagnosed as osteoporosis patients by routine diagnosis. It is important to identify these individuals, to avoid inappropriate treatment with antiresorptive drugs.

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Titel: Musculoskeletal pain and muscular weakness as the main symptoms of adult hypophosphatasia in a Spanish cohort: clinical characterization and identification of a new ALPL gene variant
verfasst von: Pilar Calmarza
Carlos Lapresta
María Martínez García
José Ochoa
Paula Sienes Bailo
Javier Acha Pérez
Jesús Beltrán Audera
Eva González-Roca
Publikationsdatum: 23.06.2023
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 5/2023
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-023-01440-z

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Musculoskeletal pain and muscular weakness as the main symptoms of adult hypophosphatasia in a Spanish cohort: clinical characterization and identification of a new ALPL gene variant