Late-onset mitochondrial complex IV deficiency, nuclear type 1 associated with the SURF1 gene: a case report

Abstract Background Mitochondrial Complex IV deficiency, Nuclear Type 1, is a genetic metabolic disorder inherited in an autosomal recessive pattern, characterized by rapid and progressive neurodegeneration and encephalopathy. Case report We present a 2-year-old female patient, daughter of healthy, and consanguineous parents, born at term with normal newborn screening results. At 1 year and 7 months, she began experiencing recurrent vomiting, developmental regression, and a significant drop in weight and height percentiles. Laboratory tests revealed elevated lactate and MRI findings suggestive of mitochondrial disease. Whole-exome sequencing (WES) identified a pathogenic variant in the SURF1 gene (OMIM # 220,110) c.552del (p.Lys185Argfs*3). Discussion Mitochondrial Complex IV deficiency, Nuclear Type 1, associated with the SURF1 gene clinical symptoms include developmental delays, motor abnormalities, and recurrent episodes of metabolic crisis. The combined prevalence of mitochondrial disorder is approximately one in 4300 children, making these disorders one of the most common neurometabolic conditions in pediatrics. The late-onset in this case report, at 1 year and 7 months, represents a unique feature, as most cases manifest earlier. Conclusion The findings emphasize the need for clinicians to consider SURF1-related mitochondrial Complex IV deficiency even in patients presenting later in childhood. This case also highlights the importance of multidisciplinary management and supports further research into genotype–phenotype correlations, prognostic markers, and potential therapeutic approaches, which remain limited for this condition.