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Abstract: SA-PO314

Three Patients with Recurrent Nephrolithiasis and Heterozygous ABCC6 Mutations

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical


  • Farrell, Douglas R., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Uribarri, Jaime, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Rein, Joshua L., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by mutations in the ABCC6 gene, which encodes an ATP efflux transporter. Loss-of-function results in low extracellular PPi levels, which results in progressive ectopic deposition of CaP leading to skin papules, ocular lesions, and arterial calcification. The association between PXE and nephrolithiasis (stones) is known, though this has not been implicated in those who are heterozygous. We present three cases of recurrent stones without overt risk factors (Fig. 1), but with heterozygosity in ABCC6.

Case Description

Patient 1
45 yo F with recurrent CaP stones and nephrocalcinosis. Family history significant for mother with recurrent stones. Genetic testing showed ABCC6 heterozygous variant of uncertain significance (VUS): c.1685T>C (p.Met562Thr). Skin biopsy and retinal exam did not reveal calcification.

Patient 2
35 yo M with recurrent CaOx stones (20+) and numerous 2nd & 3rd degree relatives with stones. Genetic testing showed ABCC6 heterozygous VUS: c.933C>A (p.Phe311Leu).

Patient 3
24 yo F with recurrent CaOx/CaP stones and HTN. She had yearly stones since age 2 but an unknown family history. Genetic testing showed heterozygous for likely pathogenic variant in ABCC6: c3413G>A (P.Arg1138Gln) and heterozygous VUS for PHEX and SLC34A3, both associated with stones, without either phenotype.


We hypothesize that heterozygous ABCC6 mutations are underrecognized in recurrent stone disease, without extrarenal manifestations of PXE. Threshold for genetic testing of patients with recurrent stones without clear causes should be lowered given increasing testing availability. In vitro functional assays are underway to analyze the VUS mutations.

Metabolic workup for three patients including vitals, serum and 24 hour urine data