Succinate in dystrophic white matter: A proton magnetic resonance spectroscopy finding characteristic for complex II deficiency

Abstract

A deficiency of succinate dehydrogenase is a rare cause of mitochondrial encephalomyopathy. Three patients, 2 sisters and 1 boy from an unrelated family, presented with symptoms and magnetic resonance imaging signs of leukoencephalopathy. Localized proton magnetic resonance spectroscopy indicated a prominent singlet at 2.40ppm in cerebral and cerebellar white matter not present in gray matter or basal ganglia. The signal was also elevated in cerebrospinal fluid and could be identified as originating from the two equivalent methylene groups of succinate. Subsequently, an isolated deficiency of complex II (succinate:ubiquinone oxidoreductase) was demonstrated in 2 patients in muscle and fibroblasts. One of the sisters died at the age of 18 months. Postmortem examination showed the neuropathological characteristics of Leigh syndrome. Her younger sister, now 12 months old, is also severely affected; the boy, now 6 years old, follows a milder, fluctuating clinical course. Magnetic resonance spectroscopy provides a characteristic pattern in succinate dehydrogenase deficiency.

Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations: Further Cases and Implications for Genetic Counselling

“…In addition, the corticospinal tracts and cervical medulla were affected extensively, and pulvinar and ventral thalamic nuclei showed pathological signal in both patients. MR spectroscopy was only performed in patient 2 and revealed a succinate peak, a specific finding in complex II deficiency (Brockmann et al 2002;Ghezzi et al 2009). Recently, a distinct MRI pattern was defined for patients with SDH deficiency-related leukoencephalopathy (Helman et al 2015), with a typical progression of MRI appearance during the course of disease, allowing differentiation from other mitochondrial leukoencephalopathies.…”

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

“…18 The observed increase in fatty acid metabolic enzymes in this study may also be indicative of increased lipid turnover, possibly to replace peroxide damaged cell membrane and myelin lipids. Studies into white and gray matter abnormalities of patients with mitochondrial encephalomyopathy implied that white matter is particularly vulnerable to damage by oxidative stress, 62 and white matter abnormalities are also common in diabetes patients (69% of long-duration diabetes type I). 63 Thus, there is converging support that abnormalities in white matter within the frontal cortex of schizophrenia patients 2,23 may, in fact, be correlated with an excess of ROS.…”

The in-depth evaluation of suspected mitochondrial disease

“…Deficient respiratory chain activity produces significant increases in succinate concentration to permit its detection by MRS. In 3 patients with complex II deficiency, a very large succinate signal along with reduced NAA/Cr and increased Lac signals were observed within white matter, while only a decrease in NAA/Cr ratio was seen within cortical gray matter [45]. This highlights the importance of utilizing multivoxel acquisition, or at least using single voxels over both gray and white matter in the MRS evaluation of respiratory chain disease.…”

“…In proton MRS, the resonance of succinate overlaps with those of glutamate and glutamine [43]. Under normal conditions, the succinate peak is not visible on MRS [45]. Deficient respiratory chain activity produces significant increases in succinate concentration to permit its detection by MRS.…”