Siblings with Leigh syndrome complicated by arginine vasopressin deficiency: A case report

Background Leigh syndrome (LS) is a rare genetic neurometabolic disorder and the most common pediatric mitochondrial disease (MD). Endocrine disorders (EDs) are frequent, but arginine vasopressin deficiency (AVP-D) is rarely reported, and its clinical characteristics and pathophysiology remain unclear. Case presentation We describe siblings with genetically confirmed LS caused by a pathogenic mitochondrial DNA variant (m.9176T>C) who developed AVP-D during their clinical courses. Case 1 A male diagnosed with LS at the age of 18 months started vitamin cocktail therapy. Respiratory deterioration followed by abrupt-onset polyuria and severe hypernatremia at the age of 5 years led to a diagnosis of AVP-D. Desmopressin replacement improved urine output, but the patient died of septic shock. Case 2 A younger sister harbored the same mitochondrial gene variant and was diagnosed with LS at 10 months of age. At 21 months of age, she was admitted with pneumonia complicated by respiratory failure and required intubation. She also developed sudden-onset polyuria and hypernatremia and was diagnosed with AVP-D. Unlike her brother, she also had panhypopituitarism, likely secondary to hypoxic brain injury, and was discharged after undergoing several hormone-replacement therapies. Discussion To our knowledge, this is the first report of siblings with genetically confirmed LS complicated by AVP-D, highlighting the rare but potentially severe nature of AVP-D in LS and suggesting selective vulnerability of the hypothalamic–pituitary axis in patients with MD. Clinicians should consider AVP-D when abrupt polyuria and hypernatremia occur during the management of patients with LS.