A case report of odonto-hypophosphatasia with a novel variant in the ALPL gene

Yuji Oto; Daiki Suzuki; Tsubasa Morita; Takeshi Inoue; Akihisa Nitta; Nobuyuki Murakami; Yuuka Abe; Yoshinobu Hamada; Tomoyuki Akiyama; Tomoyo Matsubara

doi:10.1515/jpem-2023-0549

Article

A case report of odonto-hypophosphatasia with a novel variant in the ALPL gene

Yuji Oto , Daiki Suzuki , Tsubasa Morita , Takeshi Inoue , Akihisa Nitta , Nobuyuki Murakami , Yuuka Abe , Yoshinobu Hamada , Tomoyuki Akiyama and Tomoyo Matsubara

Published/Copyright: February 5, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 3

Abstract

Objectives

Hypophosphatasia (HPP) is a rare skeletal dysplasia caused by variants in the alkaline phosphatase (ALPL) gene. More than 400 pathogenic variants of the ALPL gene have been registered in the ALPL gene variant database. Here, we describe the case of a Japanese child with odonto-hypophsphatasia (odonto-HPP) and a novel ALPL variant.

Case presentation

At the age of 2 years and 1 month, he prematurely lost one deciduous tooth, with the root intact, when he fell and hit his face lightly. Three months later, he lost another adjacent deciduous tooth without incentive. His serum alkaline phosphatase (ALP) level was 72 U/L. His urine phosphoethanolamine (PEA) level was extremely high at 938 μmol/mg·Cre. The serum pyridoxal 5′-phosphaye (PLP) level was 255.9 nmol/L. Based on the clinical symptoms and laboratory findings, the patient was clinically diagnosed with odonto-HPP. Genetic analysis of the ALPL gene revealed a heterozygous variant (NM_000478.6:c.1151C>A, p.Thr384Lys).

Conclusions

We report a case of odonto-HPP with a novel variant in the ALPL gene. HPP is a rare disease, and the heterozygous mutation in the ALPL gene highlights the novelty of this case.

Keywords: odonto-hypophosphatasia; missense variant; ALPL gene

Corresponding author: Yuji Oto, Department of Pediatrics, Dokkyo Medical University Saitama Medical Center, 2-1-50 Minamikoshigaya, Koshigaya City, Saitama 343-8555, Japan, Phone: +81 48 965 1111, Fax: +81 48 965 8363, E-mail: yuji-oto@dokkyomed.ac.jp

Acknowledgments

The authors are grateful to the patient for his kind contribution to this study. We thank the patient’s parents for considering to the publication of this report. We would like to thank Editage (www.editage.jp) for English language editing.

Research ethics: Not applicable.
Informed consent: Written informed consent was obtained from the parents of the patient for the publication of this report.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

References

1. Whyte, MP. Hypophosphatasia: an overview for 2017. Bone 2017;102:15–25. https://doi.org/10.1016/j.bone.2017.02.011.Search in Google Scholar PubMed

2. Mornet, E. Hypophosphatasia. Metabolism 2018;82:142–55. https://doi.org/10.1016/j.metabol.2017.08.013.Search in Google Scholar PubMed

3. Michigami, T, Ohata, Y, Fujiwara, M, Mochizuki, H, Adachi, M, Kitaoka, T, et al.. Clinical Practice Guidelines for hypophosphatasia. Clin Pediatr Endocrinol 2020;29:9–24. https://doi.org/10.1297/cpe.29.9.Search in Google Scholar PubMed PubMed Central

4. The ALPL gene variant database. Available from: https://alplmutationdatabase.jku.at/.Search in Google Scholar

5. Rentzsch, P, Witten, D, Cooper, GM, Shendure, J, Kircher, M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 2019;8:D886–94. https://doi.org/10.1093/nar/gky1016.Search in Google Scholar PubMed PubMed Central

6. Watanabe, A, Karasugi, T, Sawai, H, Naing, BT, Ikegawa, S, Orimo, H, et al.. Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasia in Japanese and effects of the mutation on heterozygous carriers. J Hum Genet 2011;56:166–8. https://doi.org/10.1038/jhg.2010.161.Search in Google Scholar PubMed

7. Michigami, T, Tachikawa, K, Yamazaki, M, Kawai, M, Kubota, T, Ozono, K. Hypophosphatasia in Japan: ALPL mutation analysis in 98 unrelated patients. Calcif Tissue Int 2020;106:221–31. https://doi.org/10.1007/s00223-019-00626-w.Search in Google Scholar PubMed

8. Oyachi, M, Harada, D, Sakamoto, N, Ueyama, K, Kondo, K, Kishimoto, K, et al.. A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: clinical course and review of the literature. Clin Pediatr Endocrinol 2018;27:179–86. https://doi.org/10.1297/cpe.27.179.Search in Google Scholar PubMed PubMed Central

9. Sugiyama, Y, Watanabe, T, Tajika, M, Matsuhashi, T, Shimura, M, Fushimi, T, et al.. A Japanese single-center experience of the efficacy and safety of asfotase alfa in pediatric-onset hypophosphatasia. Orphanet J Rare Dis 2022;17:78. https://doi.org/10.1186/s13023-022-02230-y.Search in Google Scholar PubMed PubMed Central

10. Hofmann, C, Girschick, H, Mornet, E, Schneider, D, Jakob, F, Mentrup, B. Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia. Eur J Hum Genet 2014;10:1160–4. https://doi.org/10.1038/ejhg.2014.10.Search in Google Scholar PubMed PubMed Central

11. Kadota, T, Ochiai, M, Okawa, R, Nakano, K. Different dental manifestations in sisters with the same ALPL gene mutation: a report of two cases. Children 2022;9:1850. https://doi.org/10.3390/children9121850.Search in Google Scholar PubMed PubMed Central

12. Takagi, M, Kato, S, Muto, T, Sano, Y, Akiyama, T, Takagi, J, et al.. Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report. Clin Pediatr Endocrinol 2020;29:115–8. https://doi.org/10.1297/cpe.29.115.Search in Google Scholar PubMed PubMed Central

13. Okawa, R, Kokomoto, K, Nakano, K. Dental effects of enzyme replacement therapy in case of childhood-type hypophosphatasia. BMC Oral Health 2021;27:323.10.1186/s12903-021-01673-2Search in Google Scholar PubMed PubMed Central

14. Whyte, MP. Hypophosphatasia – aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 2016;12:233–46. https://doi.org/10.1038/nrendo.2016.14.Search in Google Scholar PubMed

Received: 2023-12-13

Accepted: 2024-01-16

Published Online: 2024-02-05

Published in Print: 2024-03-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0549

Keywords for this article

odonto-hypophosphatasia; missense variant; ALPL gene