Introduction: Leigh syndrome is a rare mitochondrial disorder characterized by subacute necrotizing encephalomyelopathy, resulting from defects in mitochondrial respiratory enzymes or pyruvate dehydrogenase complex. Symptoms can manifest in infancy, childhood, or adulthood. We present a case of a 7-month-old girl initially misdiagnosed with septic shock but was later found to have Leigh encephalomyelopathy due to MT-ATP6 deficiency.

Case presentation: A 7-month-old girl was admitted with fever, drowsiness, and wheezing, initially diagnosed with septic shock. She had a history of parental consanguinity and hypotonia. Physical examination revealed unconsciousness, miotic pupils, and respiratory distress. Initial laboratory tests showed significant metabolic acidosis and elevated lactate, creatine kinase, and ammonia levels. The patient was treated for sepsis and shock, but her condition worsened with elevated lactate and liver transaminases, eventually leading to hypertrophic cardiomyopathy and multiorgan failure. Her basic metabolic scans showed extremely low citrulline levels, whole-exome sequencing analysis did not show any pathologic change in nuclear genome, and mitochondrial genome analysis revealed an MT-ATP homoplasmic variant. She passed away on the 22nd day of hospitalization.

Discussion/conclusion: While mitochondrial disorders are broadly acknowledged for their phenotypic diversity, it is essential to note that specific disorders, such as Leigh syndrome, display distinctive presentations with varying degrees of severity. Factors such as the percentage of homoplasmy contribute to the variability in manifestations. Notably, MT-ATP6-associated Leigh syndrome is predominantly characterized by an early onset, typically occurring before the age of 2 years. Low citrulline levels have been observed in approximately 90% of patients with MT-ATP6-related disorders, distinguishing them from other mitochondrial disorders. The exact mechanisms underlying this specific metabolic alteration are not fully understood, but it could be linked to disruptions in the mitochondrial energy production process. The mitochondria are essential for various metabolic pathways, including the urea cycle, where citrulline is involved. The association between low citrulline levels and MT-ATP6-related disorders raises the possibility of using citrulline as a potential biomarker for disease identification. MT-ATP6 defects should be kept in mind in cases with mitochondrial disease and low plasma citrulline levels.