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Clinical Significance of Hypophosphatasemia in Children

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Abstract

Low serum alkaline phosphatase (sALP)—hypophosphatasemia—is a characteristic of hypophosphatasia (HPP), but related to several clinical conditions. Here, we evaluated the frequency, persistency and the etiology of hypophosphatasemia in children. In retrospective analyses of sALP measurements from children, evaluated according to in-house constructed age- and sex-specific reference ranges, patients with no normal sALP measurement (Unresolved hypophosphatasemia) were invited for reanalysis. Prospectively, ALP substrates, pyridoxal-5-phosphate (PLP), and phosphoethanolamine (PEA) were measured in patients with persistent hypophosphatasemia. Radiographs and ALPL gene sequencing for HPP were performed to the cases with elevated PEA and/or PLP. From 130,340 sALP measurements of 93,162 patients, hypophosphatasemia was detected in 1404 samples from 867 patients (0.9%). Among them, 745 had at least one normal sALP values in laboratory records, grouped as transient hypophosphatasemia. 75 out of 122 patients with unresolved hypophosphatasemia could be reanalyzed for sALP, of whom PLP and PEA measurements were required in 37 due to persistent hypophosphatasemia. Both PEA and PLP were elevated in 4 patients, and ALPL gene analysis showed heterozygous mutations in 3 patients and homozygous in 1 patient. Elevated PEA with normal PLP were detected in 3 patients, and one had a heterozygous ALPL mutation. Anemia was the most common diagnosis, and upper respiratory tract infections and chronic diseases were more common in transient and unresolved hypophosphatasemia, respectively. In conclusion, reflected persistent hypophosphatasemia frequency was 1/1552 (0.06%) in this large pediatric cohort and, ALPL gene mutations were detected in 13.5% (5/37) of the studied cases. Although biochemical hypophosphatasemia is not uncommon, clinically significant HPP is rare.

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Abbreviations

ALP:

Alkaline phosphatase

TNSALP:

Tissue-nonspecific ALP, ALPL gene

HPP:

Hypophosphatasia

PPi:

Inorganic pyrophosphate

PLP:

Pyridoxal-5-phosphate

PEA:

Phosphoethanolamine

Ca:

Calcium

PO4 :

Phosphate

PTH:

Parathyroid hormone

Cre:

Creatinine

S:

Serum

U:

Urine

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Acknowledgements

We are thankful to Alexion Pharmaceuticals, Inc for providing fund for ALP substrates and genetic analysis of the patients.

Funding

Alexion Pharmaceuticals, Inc for providing fund for ALP substrates and genetic analysis of the patients.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Pediatrics, Marmara University School of Medicine, Istanbul, Turkey

    Rana Bayramli, Tulay Guran, Zeynep Atay, Serpil Bas, Abdullah Bereket & Serap Turan

  2. Department of Biochemistry, Marmara University School of Medicine, Istanbul, Turkey

    Tulay Cevlik & Goncagul Haklar

  3. Pediatric Endocrinology and Diabetes, Marmara University Hospital, Fevzi Cakmak Mh., Muhsin Yazicioglu Cd.No 41, Ustkaynarca/Pendik, 34899, Istanbul, Turkey

    Serap Turan

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  1. Rana Bayramli
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  2. Tulay Cevlik
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  3. Tulay Guran
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  4. Zeynep Atay
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  6. Goncagul Haklar
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  7. Abdullah Bereket
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Correspondence to Serap Turan.

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Conflict of interest

Rana Bayramli, Tulay Cevlik, Tulay Guran, Zeynep Atay, Serpil Bas, Goncagul Haklar, Abdullah Bereket, and Serap Turan declared that have no conflict of interest to declare.

Human and Animal Rights and Informed Consent

This study was approved by the Marmara University Medical Faculty Research Ethic Committee (Approval number: 09.2015.330), and the consent forms were obtained from all subjects before participating in to the study.

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Bayramli, R., Cevlik, T., Guran, T. et al. Clinical Significance of Hypophosphatasemia in Children. Calcif Tissue Int 106, 608–615 (2020). https://doi.org/10.1007/s00223-020-00677-4

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  • DOI: https://doi.org/10.1007/s00223-020-00677-4

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