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Clinical, radiographic and biochemical characteristics of adult hypophosphatasia

Abstract

Summary

In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms.

Introduction

Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP.

Methods

We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients.

Results

Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP.

Conclusion

Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.

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Acknowledgments

Authors’ roles: Study design: TS, HM, FB, WR and MA. Study conduct: TS, HM and FB. Data collection: HM, TR, JH and TH. Data analysis: TS. Drafting manuscript: TS, HM and FB. Approving final version of manuscript: TS, HM, TS, TW, JH, WR, MA and FB. TS takes responsibility for the integrity of the data analysis.

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Corresponding author

Correspondence to T. Schmidt.

Ethics declarations

The local ethics committee approved the study (PV5272).

Conflict of interest

Tobias Schmidt, Haider Mussawy, Tim Rolvien, Thelonius Hawellek, Jan Hubert, Wolfgang Rüther, Michael Amling and Florian Barvencik declare that they have no conflict of interest. F.B. receives speaker and consultant fees from Alexion, Lilly, and MSD. M.A. receives speaker and consultant fees from Merck.

Electronic supplementary material

Supplemental Figure 1
figure 4

a) Z-scores and T-scores of left femoral neck of patients with a history of fracture are compared to patients without fractures; b) Z-scores and T-scores of lumbar spine of patients with a history of fracture are compared to patients without fractures (GIF 23 kb)

Supplemental Figure 2
figure 5

Ten patients received low-dose vitamin D substitution (500 I.E.–1000 I.E.) and were regularly monitored for serum levels of 25-OH-D, calcium and phosphate. Mean values of absolute changes in serum levels ±SD (GIF 17 kb)

Supplemental Table 1

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Supplemental Table 2

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High resolution image (TIFF 680 kb)

High resolution image (TIFF 627 kb)

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Schmidt, T., Mussawy, H., Rolvien, T. et al. Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. Osteoporos Int 28, 2653–2662 (2017). https://doi.org/10.1007/s00198-017-4087-z

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  • DOI: https://doi.org/10.1007/s00198-017-4087-z

Keywords

  • Alkaline phosphatase
  • ALPL
  • Pyridoxal-5-phosphate
  • Rare bone diseases