SUCLA2 Arg407Trp mutation can cause a nonprogressive movement disorder – deafness syndrome

Abstract

SUCLA2 is a component of mitochondrial succinate‐CoA ligase and nucleotide diphosphokinase activities. Its absence results in Krebs cycle failure, mitochondrial DNA depletion, and a childhood‐fatal encephalomyopathy. We describe a purely neurologic allelic form of the disease consisting of deafness, putamenal hyperintensity on MRI and a myoclonic‐dystonic movement disorder unchanging from childhood into, so far, the late fourth decade. We show that succinate supplementation circumvents the Krebs cycle block, but does not correct the neurologic disease. Our patients’ Arg407Trp mutation has been reported in children with (yet) no MRI abnormalities. It remains possible that early succinate supplementation could impact the disease.

Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas

“…A previous study showed that IDH1 and IDH2 mRNA expression is notably reduced in the skin surrounding hidradenitis suppurativa lesions (56). Deletion of SUCLA2 leads to TCA circulatory failure, mitochondrial DNA depletion and fatal childhood encephalomyopathy (57). In addition, MDH2 silencing promotes ovarian cancer cell proliferation in vitro and in vivo (58).…”

Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens

“…PCK1 is the first rate-limiting enzyme in liver gluconeogenesis and catalyzes the conversion of oxaloacetate to phosphoenolpyruvate; hypoxia can upregulate PCK1 to trigger gluconeogenesis to glycogenolysis [ 34 , 35 ]. SUCLA2 encodes the TCA cycle enzyme ADP-specific succinate-CoA ligase (β subunit) and is critical for mitochondrial succinate-CoA ligase and nucleotide diphosphokinase activities [ 36 ]. SUCLA2 can also regulate the succinylation and enzyme activity of glutaminase under oxidative stress, thereby enhancing the level of glutamine metabolism [ 37 ].…”