Leigh syndrome with nephrotic syndrome

Leigh syndrome with nephrotic syndrome (Orphanet code 255249) is an extremely rare mitochondrial disorder that combines the features of Leigh syndrome — a severe progressive neurological condition — with nephrotic syndrome, a kidney disorder characterized by massive protein loss in the urine. Leigh syndrome (also known as subacute necrotizing encephalomyelopathy) typically involves bilateral symmetric lesions in the brainstem and basal ganglia, leading to progressive neurological deterioration. When combined with nephrotic syndrome, patients experience both devastating central nervous system disease and significant renal dysfunction. The neurological features of this condition include psychomotor regression, hypotonia, dystonia, respiratory abnormalities, feeding difficulties, and failure to thrive. The nephrotic syndrome component manifests with proteinuria, hypoalbuminemia, edema, and progressive kidney disease. The underlying pathology is thought to involve defects in mitochondrial energy metabolism affecting both the brain and kidneys, which are organs with high metabolic demands. This combination has been reported in association with coenzyme Q10 (CoQ10) biosynthesis defects, particularly mutations in genes involved in the CoQ10 pathway. There is no cure for this condition. Treatment is largely supportive and may include management of seizures, nutritional support, respiratory care, and treatment of nephrotic syndrome with standard nephrology approaches. In cases linked to CoQ10 deficiency, supplementation with coenzyme Q10 has been attempted and may provide some benefit, particularly for the renal manifestations, though neurological outcomes remain poor. Early diagnosis and initiation of CoQ10 supplementation, when applicable, may improve renal prognosis. The overall prognosis is generally severe, with significant morbidity and early mortality.

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