Early-onset kidney failure in a girl with autosomal dominant tubulointerstitial kidney disease due to a de novo UMOD variant

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by renal tubular and interstitial abnormalities and slow progressive loss of kidney function. Patients with ADTKD rarely progress to kidney failure in early childhood. A 7-year-old Japanese girl was admitted to the hospital due to afebrile seizures and was later diagnosed with Panayiotopoulos syndrome. Blood examinations showed that she had a serum creatinine level of 1.57 mg/dL (Cr-eGFR 28 mL/min/1.73 m²), consistent with chronic kidney disease stage 4. Ultrasonography showed bilateral small to normal-sized kidneys, with increased renal parenchymal echogenicity, poor corticomedullary differentiation, and small cysts. A panel exome sequencing targeting 187 genes identified a de novo pathogenic variant c.172G > T, p.Gly58Cys in the EGF-like domain 1 of the UMOD gene. Her parents did not possess this variant, leading to the diagnosis of a sporadic case of ADTKD-UMOD. Variants in the EGF-like domain 1 may lead to early progression to kidney failure. ADTKD-UMOD should be listed as a differential diagnosis of progressive kidney failure in early childhood, even in the absence of a family history.