Abstract
BACKGROUND: Kearns-Sayre syndrome (KSS) is a mitochondrial genetic disorder characterized by progressive external ophthalmoplegia, short stature, atrioventricular block, and proximal renal tubular dysfunction. While Fanconi syndrome is a recognized renal manifestation of KSS, it is rare as the initial presenting feature. This report describes the clinical and genetic features of a child with KSS who initially presented with Fanconi syndrome. CASE DESCRIPTION: A 10-year-old girl, initially diagnosed with Fanconi syndrome at 3 years of age, exhibited growth retardation by age 5 years and bilateral ptosis by age 8 years. In July 2022, her age of 10 years, she developed diabetes mellitus and third-degree atrioventricular block. The patient presented for medical evaluation. Upon examination, she was found to have sensorineural hearing loss, hyperlactatemia, elevated cerebrospinal fluid protein, decreased folate levels, and renal insufficiency. Muscle biopsy revealed ragged red fibers, and mitochondrial gene analysis confirmed the diagnosis of KSS. Whole-exome sequencing identified a heterozygous mutation in the DNA2 gene (c.865C>T, p.R286X) along with a 7,521-base pair mitochondrial DNA deletion. Symptoms improved with nutritional mitochondrial therapy. CONCLUSIONS: Mitochondrial mutations may contribute to the development of Fanconi syndrome. Fanconi syndrome may present as the initial manifestation of KSS. KSS should be considered in pediatric patients presenting with Fanconi syndrome and extrarenal manifestations, such as ptosis.