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Abstract: PO2311

Dent Disease Phenotype Caused by Immunodysregulation Polyendocrinopathy Enteropathy X-Linked (IPEX) Syndrome: Due to Anti-Tubular Basement Membrane Antibody Disease

Session Information

Category: Trainee Case Report

  • 1700 Pediatric Nephrology

Authors

  • Dandamudi, Raja, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, United States
  • Hruska, Keith A., Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, United States
Introduction


Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) recessive disorder caused by loss-of-function mutations forkhead box protein 3 gene (FOXP3) transcription factor affecting the function of circulating regulatory T cells .
Previously described renal manifestations were immune complex deposition in a membranous- pattern and interstitial nephritis.
Here we report novel renal manifestations of IPEX syndrome.

Case Description

5-year-old male ipresented at the end of the first month of life, with type 1 diabetes mellitus, hypothyroidism, and chronic diarrhea and diagnosed by IPEX syndrome by c.434C>T; p. Ala 145Val mutations in the FOXP3 gene. He underwent stem cell transplant at 6 months of age from a fully matched unrelated donor. Post stem cell transplant he has had mixed chimerism with low but relatively stable donor T cells.

He remained relatively stable until 4 years of age when he presented with the clinical picture of Dent’s disease: nephrocalcinosis, tubular proteinuria, Fanconi syndrome (proximal RTA, phosphaturia , calciuria, glycosuria and aminoaciduria) and renal insufficiency.No disease-causing mutations in CLCN5 gene or the OCRL1 gene were identified on genetic testing.

Renal biopsy demonstrated non-sclerotic glomeruli with no capillary loop spike formation, no crescent formation, no endocapillary proliferation,or segmental necrosis.Immunofluorescence showed tubular basement membranes stain with IgG, C3, kappa and lambda. Glomerular basement membranes were negative.Tubular basement membranes show extensive small electron dense deposits without substructure.

Discussion

In this case report we presented child with confirmed IPEX syndrome with nephrotic-range tubular proteinuria, proximal RTA, phosphaturia, calciuria, medullary nephrocalcinosis, and renal insufficiency, in addition to the classical triad of enteropathy, dermatitis and polyendocrinopathy.
Our report is the first to document the anti-tubular basement disease clinically manifesting as the Dent’s disease phenotype in association with IPEX syndrome.