AUTOSOMAL DOMINANT TUBULOINTERSTITIAL KIDNEY DISEASE DUE TO MUC1 MUTATION: THE CASE OF A FAMILY WITH AN EXTREMELY RARE DISEASE IN LATIN AMERICA

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is a group of rare monogenic disorders with undetermined prevalence (1). The MUC1 subtype (ADTKD-MUC1) represents about 25% of genetically confirmed cases (2). End-stage kidney disease (ESKD) onset typically occurs between ages 45–50, with progression rates varying by the level of mutant MUC1 (MUC1fs) accumulation in renal tubular cells and associated endoplasmic reticulum stress, than to age or sex, explaining the phenotypic heterogeneity observed among carriers (10). The disease is caused by a cytosine duplication in a variable number tandem repeat (VNTR) region of the MUC1 gene (chromosome 1q22), leading to intracellular buildup of MUC1fs (13). There is no specific treatment, but kidney transplantation is curative, with graft survival similar to other etiologies (16). We report the first genetically confirmed case of ADTKD-MUC1 in Chile and the second in South America.

After informed consent, a multidisciplinary team led by a nephrologist reviewed the clinical records of a patient with an extremely rare condition in latin population. A literature review was also conducted.

A 19-year-old man with no prior medical history was evaluated for early CKD. Family history revealed multiple maternal relatives with ESKD of unknown cause: his grandmother died at 40, his mother received a transplant, an aunt is on dialysis, and his sister is under evaluation for renal tubular acidosis—suggesting autosomal dominant inheritance. Kidney biopsy showed 40% tubular atrophy and 30% interstitial fibrosis. Electron microscopy initially raised suspicion for Fabry disease, but GLA gene testing was negative. Further testing at Wake Forest University (USA) identified a pathogenic cytosine duplication in the VNTR region of the MUC1 gene, confirming ADTKD-MUC1. The patient’s renal function continued to decline with bland urinalysis; he is receiving conservative management and being evaluated for transplantation. Genetic testing confirmed the same mutation in his maternal aunt; other affected relatives are undergoing evaluation.

This case highlights the diagnostic challenge of hereditary nephropathies with silent clinical presentation, and reflect the trend of exert every effort to identify etiology of renal failure. A family history of ESKD, bland urinalysis, and biopsy showing nonspecific interstitial fibrosis should raise suspicion for ADTKD—especially when initial genetic panels are inconclusive. Identifying a MUC1 mutation not only confirms the diagnosis but reshapes the approach to familial screening, prognosis, and therapeutic approach. ADTKD-MUC1 exemplifies key challenges in hereditary kidney diseases: insidious progression, nonspecific histology, and the need for advanced molecular diagnostics. Increasing awareness and access to genetic testing are crucial in Latin America, where such resources remain scarce. This case underscores the importance of family screening and early diagnosis to optimize care for rare kidney disorders.

This abstract was also submitted for the XLII Chilean Congress of Nephrology, Hypertension, and Transplantation, and its submission counts on the support of the Chilean Society of Nephrology.