| Summary: | <p>Abstract</p> <p>Background</p> <p>Deficiency of complex II (succinate dehydrogenase, SDH) represents a rare cause of mitochondrial disease and is associated with a wide range of clinical symptoms. Recently, mutations of <it>SDHAF1,</it> the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify <it>SDHAF1</it> mutations in further patients and to delineate the clinical phenotype.</p> <p>Methods</p> <p>In a retrospective data collection study we identified nine children with biochemically proven complex II deficiency among our cohorts of patients with mitochondrial disorders. The cohort comprised five patients from three families affected by SDH-defective infantile leukoencephalopathy with accumulation of succinate in disordered cerebral white matter, as detected by <it>in vivo</it> proton MR spectroscopy. One of these patients had neuropathological features of Leigh syndrome. Four further unrelated patients of the cohort showed diverse clinical phenotypes without leukoencephalopathy. <it>SDHAF1</it> was sequenced in all nine patients.</p> <p>Results</p> <p>Homozygous mutations of <it>SDHAF1</it> were detected in all five patients affected by leukoencephalopathy with accumulated succinate, but not in any of the four patients with other, diverse clinical phenotypes. Two sisters had a mutation reported previously, in three patients two novel mutations were found.</p> <p>Conclusion</p> <p>Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to <it>SDHAF1</it> mutations.</p>
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