To investigate clinical characteristics and prognosis of children with autosomal dominant optic atrophy (ADOA) complicated with end-stage renal disease caused by SSBP1 gene mutation.

On March 31, 2021, a pediatric patient (Patient 1) with chronic kidney disease of unknown etiology who was treated at Xi′an Children′s Hospital was selected in this study. A retrospective analysis was performed to collect the clinical data of Patient 1, and whole-exome sequencing (WES) together with Sanger sequencing validation results were obtained. The pathogenicity of the detected variants was evaluated in accordance with the guidelines established by the American College of Medical Genetics and Genomics (ACMG). This study adhered to the requirements of the revised 2013 Declaration of Helsinki of the World Medical Association. Informed consent was obtained from the guardians of Patient 1.

① Patient 1 was a 6-year-6-month-old male who presented with a 1-year history of short stature and a 1-month history of abnormal renal function. He was admitted to the Department of Nephrology at Xi′an Children′s Hospital on March 31, 2021. Upon admission, auxiliary examinations revealed a blood urea level of 15.26 mmol/L, a serum creatinine level of 172 μmol/L, and an estimated glomerular filtration rate (GFR) of 31.05 mL/(min·1.73 m²), accompanied by mild metabolic acidosis and mild anemia. Cranial MRI indicated bilateral cerebellar atrophy, and visual acuity in both eyes was 0.06. Whole-exome sequencing (WES) identified a heterozygous c. 320G>A (p.Arg107Gln) variant in the SSBP1 gene, which was confirmed by Sanger sequencing to be of paternal origin. During follow-up, the GFR of patient 1 declined to 13.89 mL/(min·1.73 m²) by the age of 10 years and 3 months, at which point peritoneal dialysis was initiated. ② A literature review identified 14 reported patients with ADOA caused by SSBP1 gene variants and accompanied by renal impairment, including 10 males and 4 females. All patients had disease onset during infancy or childhood; however, diagnosis was delayed in all cases. Apart from renal involvement, the most common additional manifestations were sensorineural hearing loss and neurological symptoms. Among the identified variants, the heterozygous missense mutation c. 320G>A was the most frequent (8/14).

For pediatric patients presenting with optic atrophy accompanied by hearing loss, neurological involvement, and renal impairment-particularly when there is a positive family history-genetic testing should be performed when necessary to confirm the diagnosis.