Seyda et al. (2001) reported a male infant, born of first-cousin East Indian parents, who developed epileptic seizures associated with elevated levels of serum glycine and cerebrospinal fluid (CSF) glycine at age 4 months. At age 6 months, ... Seyda et al. (2001) reported a male infant, born of first-cousin East Indian parents, who developed epileptic seizures associated with elevated levels of serum glycine and cerebrospinal fluid (CSF) glycine at age 4 months. At age 6 months, he was developmentally delayed, and subsequently developed dilated cardiomyopathy and epileptic encephalopathy. He had recurrent vomiting, lethargy, respiratory distress, and hepatomegaly. At age 7 months, he became acidotic. His CSF glycine rose to very high levels, and he died at 11 months of age. Studies of skin fibroblasts showed lactate/pyruvate ratios that were 6 times greater than those of controls. Fibroblasts showed decreased activity of the pyruvate dehydrogenase complex, branched-chain alpha-keto acid dehydrogenase (608348), and mitochondrial respiratory chain complexes. In contrast, the activities of fibroblast pyruvate carboxylase (608786), mitochondrial aconitase (100850), and citrate synthase (118950) were normal.
In the East Indian patient with MMDS2 reported by Seyda et al. (2001), Cameron et al. (2011) identified a homozygous truncating mutation in the BOLA3 gene (613183.0001). Transduction of fibroblast lines with retroviral vectors expressing the mitochondrial, but ... In the East Indian patient with MMDS2 reported by Seyda et al. (2001), Cameron et al. (2011) identified a homozygous truncating mutation in the BOLA3 gene (613183.0001). Transduction of fibroblast lines with retroviral vectors expressing the mitochondrial, but not the cytosolic, isoform of BOLA3 corrected the defects in respiratory chain and oxoacid dehydrogenase complex function. The results indicated that BOLA3 plays an essential role in the production of iron-sulfur (Fe-S) clusters for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases and for the assembly of the respiratory chain complexes.