Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome

Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome (also known as Sengers syndrome) is an extremely rare multisystem disorder caused by defects in mitochondrial energy metabolism. The condition is characterized by the combination of congenital cataracts (clouding of the eye lenses present at birth), hypertrophic cardiomyopathy (abnormal thickening of the heart muscle), skeletal muscle myopathy related to mitochondrial dysfunction, and lactic acidosis. The syndrome is caused by biallelic pathogenic variants in the AGK gene (acylglycerol kinase), which plays a role in mitochondrial lipid metabolism and the assembly of the mitochondrial adenine nucleotide translocator. The disease primarily affects the eyes, heart, and skeletal muscles. Patients typically present in the neonatal or infantile period with bilateral cataracts and signs of cardiac dysfunction. The hypertrophic cardiomyopathy can be severe and is a major determinant of prognosis, as it may lead to heart failure. Skeletal muscle involvement manifests as exercise intolerance and weakness, with muscle biopsies showing mitochondrial abnormalities. Laboratory findings often include elevated levels of lactic acid in the blood. A characteristic biochemical finding is markedly reduced levels of mitochondrial adenine nucleotide translocator in muscle tissue. There is no specific curative treatment for Sengers syndrome. Management is supportive and multidisciplinary, including surgical removal of cataracts, cardiac monitoring and treatment of heart failure symptoms, and physical therapy for muscle weakness. The prognosis varies; a severe neonatal form can lead to early death from cardiac failure, while a milder form allows survival into adulthood. Genetic counseling is recommended for affected families.

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