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

Endocrine. 2010 Apr;37(2):244-8. doi: 10.1007/s12020-009-9299-3. Epub 2010 Jan 5.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcinosis / blood*
  • Calcinosis / diagnostic imaging
  • Calcinosis / genetics*
  • Calcium Phosphates / urine
  • DNA Mutational Analysis
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / genetics*
  • Humans
  • Intestinal Absorption / physiology
  • Lung Diseases / blood*
  • Lung Diseases / diagnostic imaging
  • Lung Diseases / genetics*
  • Male
  • Pulmonary Alveoli / diagnostic imaging
  • Pulmonary Alveoli / metabolism
  • Radiography
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / genetics

Substances

  • Calcium Phosphates
  • FGF23 protein, human
  • SLC34A2 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIb
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • calcium phosphate