SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome: a case report and review of literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient, and review the latest clinical research reports.</p><p><b>METHOD</b>Clinical, laboratory and genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by department of Neurology, Beijing Children's Hospital in November, 2013 were reported, and through taking "SUCLA2" as key words to search at CNKI, Wanfang, PubMed and the Human Gene Mutation Database (HGMD) professional to date, the clinical characteristics of 24 reported cases of SUCLA2-related encephalomyopathic MDS in international literature in combination with our case were analyzed.</p><p><b>RESULT</b>(1) The patient was 5 years and 9 months old, born as a term small for gestational age infant whose birth weight was 2 400 g, and presented since birth with severe muscular hypotonia, feeding difficulties, failure to thrive, psychomotor retardation and hearing impairment. Until now, he still showed severe developmental retardation, together with muscular atrophy, thoracocyllosis and scoliosis, and facial features. The patient is the first born from consanguineous healthy parents, whose relationship is cousins. Laboratory tests showed urinary excretion of mild methylmalonic acid (MMA), elevated plasma lactate concentration, and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral T2 hyperintensities in bilateral caudate nuclei and putamen. By Next-Generation Sequencing (NGS), we identified a novel homozygous missense mutation (c.970G > A) in the SUCLA2 in a highly conserved amino acid residue. (2) The total number was only 25 with a male to female ratio of 14: 11, and age of onset of 23 was 0-4 months. The most common clinical features in patients with SUCLA2 mutation were permanent hypotonia, muscle atrophy, psychomotor retardation and scoliosis or kyphosis. Frequent signs included hearing impairment, hyperkinesia, dystonia or athetoid movements, feeding difficulties, growth retardation and ptosis or ophthalmoplegia. Epilepsy was occasionally observed. The combination of lactic acidemia, mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling were characteristic markers. MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei). Nineteen patients originated from Europe, with 13 of whom originated from Faroe Islands that carry a homozygous mutation (c.534+1G>A) in SUCLA2.</p><p><b>CONCLUSION</b>SUCLA2-related encephalomyopathic MDS is characterized by onset of severe hypotonia in early infancy, feeding difficulties, growth retardation, psychomotor retardation and hearing impairment. Metabolic findings usually include lactic acidemia, mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei). SUCLA2 pathogenic mutations would confirm the diagnosis.</p>

Deficiency of succinic dehydrogenase or succinyl-coA synthetase enhances the production of 5-aminolevulinic acid in recombinant Escherichia coli / 生物工程学报

5-aminolevulinic acid (ALA), a precursor for biosynthesis of pyrrole compounds in living organisms, has been widely used in agriculture and medical photodynamics therapy and is regarded as a promising value-added bio-based chemical. In the previous investigations on ALA production with recombinant Escherichia coli expressing heterogenous C4 pathway gene, LB media supplemented with glucose and ALA precursors succinate and glycine is widely used, leading to high production cost. Succinate participates in ALA biosynthesis in a form of succinyl-CoA. In this study, genes involved in succinyl-CoA consumption, sdhAB (encoding succinic dehydrogenase) or sucCD (encoding succinyl-CoA synthetase) of E. coli MG1655 was knocked out and tested for ALA accumulation. In comparison with the recombinant E. coli strain expressing heterogenous ALA synthetase, the sdhAB- or sucCD-deficient strain accumulate 25.59% and 12.40%, respectively, more ALA in a 5 L fermentor using a defined synthetic medium with glucose as main carbon source and without supplementation of succinate, providing a novel cost-effective approach for industrial production of ALA.