Rare forms of autosomal dominant tubulointerstitial kidney disease in children: a retrospective case series from Oman.

BACKGROUND

Autosomal dominant tubulointerstitial kidney disease (ADTKD) represents a genetically heterogeneous group of disorders. UMOD and MUC1 are the most frequently reported causes, while HNF1B-related disease, though relatively common globally, along with rarer genes such as REN and SEC61A1, remains underrecognized in pediatric populations from regions with limited access to systemic genetic testing, including the Middle East.

METHODS

We conducted a retrospective case series (2010-2024) at two tertiary pediatric nephrology centers in Oman. Children with genetically confirmed rare ADTKD variants were included. Clinical, biochemical, imaging, and histopathological data were analyzed.

RESULTS

Five patients from three unrelated families were identified. Three siblings harbored a heterozygous REN variant (c.49 T > C; p.Trp17Arg), presenting with early-onset anemia, hyperkalemia, metabolic acidosis, and hyperuricemia. Notably, two siblings exhibited significant hypomagnesemia, an underreported feature. A 16-year-old girl with a SEC61A1 variant (c.554C > G; p.Thr185Ser) presented with epilepsy, microcephaly, hypomagnesemia, and CKD. Epilepsy has not been previously associated with ADTKD-SEC61A1. A 13-year-old boy with a pathogenic HNF1B variant (c.541C > T; p.Arg181*) manifested renal cysts, hypomagnesemia, proteinuria, and maturity-onset diabetes of the young (MODY).

CONCLUSIONS

This series expands the phenotypic spectrum of rare pediatric ADTKD. We highlight hypomagnesemia as a potential feature of REN-related disease and we describe a previously unreported co-occurrence of epilepsy in a child with SEC61A1-related ADTKD. Our findings underscore the importance of early genetic testing for accurate diagnosis, targeted management, and family counseling in children with suggestive renal and extrarenal features.