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Open Access Research

Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency

Andreas Ohlenbusch1*, Simon Edvardson2, Johannes Skorpen3, Alf Bjornstad4, Ann Saada5, Orly Elpeleg5, Jutta Gärtner1 and Knut Brockmann1*

Author Affiliations

1 Department of Pediatrics and Pediatric Neurology, Georg August University, Robert Koch Str. 40, Göttingen, 37075, Germany

2 Pediatric Neurology Unit, Hadassah, Hebrew University Medical Center, Jerusalem, Israel

3 Department of Pediatric Medicine, Child Habilitation Unit, Ålesund Hospital, Ålesund, Norway

4 Department of Pediatrics, Drammen Sykehus, Drammen, Norway

5 The Department of Genetic and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem, Israel

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Orphanet Journal of Rare Diseases 2012, 7:69  doi:10.1186/1750-1172-7-69

Published: 20 September 2012

Abstract

Background

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 SDHAF1, the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype.

Methods

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 in vivo 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. SDHAF1 was sequenced in all nine patients.

Results

Homozygous mutations of SDHAF1 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.

Conclusion

Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to SDHAF1 mutations.

Keywords:
Succinate dehydrogenase; Leukoencephalopathy; SDHAF1; Leigh syndrome; Complex II deficiency; Assembly factor