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Mutation analysis and serum FGF23 level in a patient with pulmonary alveolar microlithiasis

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Abstract

Pulmonary alveolar microlithiasis (PAM) is a rare, hereditary disorder characterized by ectopic formation of calcium-phosphate microliths in the alveolar space. PAM has been reported to arise from inactivating mutations in SLC34A2, encoding a sodium-dependent phosphate co-transporter essential for phosphate transport in the lungs and small intestine. Serum levels of the phosphaturic hormone fibroblast growth factor-23 (FGF23) in PAM have not been determined. Our objectives were to investigate the genetic etiology and circulating level of FGF23 in a 50-year-old male with clinical characteristics of PAM and extra-pulmonary calcifications. The SLC34A2 and FGF23 genes were sequenced for mutations and serum FGF23 analyzed by ELISA. We found no disease-causing mutations or single nucleotide polymorphisms in the genes investigated. Importantly, repeated measurements revealed undetectable or markedly low serum FGF23 (<3–11 RU/ml). Surprisingly, in the face of low serum FGF23, 1,25-dihydroxy vitamin D3 level was low-normal and parathyroid hormone mildly elevated. Total 24-h urinary excretion of phosphate and calcium were low, as was fractional urinary excretion of calcium. In contrast, fractional excretion of phosphate was above normal, likely due to elevated PTH. Collectively, PAM may be a polygenic disorder that arises from mutations other than in SLC34A2. The low FGF23 level in our PAM patient supports an intestinal-bone axis, leading to decreased FGF23 expression when intestinal phosphate absorption is compromised.

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Acknowledgments

We are indebted to the patient for his participation. We also thank professor Hagiwara for valuable comments. Declaration of interest: V.B. and T.E.L. received lecture fees. H.O. has nothing to declare. Funding: This study was supported by the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Kidney Foundation and the Swedish Society of Medicine.

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Authors and Affiliations

  1. Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86, Stockholm, Sweden

    Hannes Olauson & Tobias E. Larsson

  2. Department of Cardiology, University Hospital Aachen, Aachen, Germany

    Vincent Brandenburg

  3. Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden

    Tobias E. Larsson

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  1. Hannes Olauson
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  2. Vincent Brandenburg
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  3. Tobias E. Larsson
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Correspondence to Tobias E. Larsson.

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Olauson, H., Brandenburg, V. & Larsson, T.E. Mutation analysis and serum FGF23 level in a patient with pulmonary alveolar microlithiasis. Endocr 37, 244–248 (2010). https://doi.org/10.1007/s12020-009-9299-3

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