Renal tubulopathy-encephalopathy-liver failure syndrome

Renal tubulopathy-encephalopathy-liver failure syndrome, also known as GRACILE syndrome (Growth Retardation, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death), is a severe inherited metabolic disorder primarily described in the Finnish population. It is caused by mutations in the BCS1L gene, which encodes a mitochondrial complex III assembly factor essential for cellular energy production. The disease affects multiple organ systems, most prominently the kidneys, brain, and liver. Affected infants typically present in the neonatal period with severe intrauterine growth restriction, progressive liver disease with cholestasis and iron overload, renal tubular dysfunction (Fanconi-type tubulopathy with aminoaciduria), and profound lactic acidosis reflecting mitochondrial dysfunction. Encephalopathy may develop as the disease progresses. The clinical course is typically very severe, with most affected infants dying within the first months of life. There is currently no curative treatment for this condition. Management is supportive and focuses on addressing metabolic acidosis, nutritional support, and managing organ-specific complications. The prognosis remains extremely poor despite intensive supportive care. Genetic counseling is recommended for affected families, and prenatal diagnosis is possible when the familial mutation is known.

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