title: Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria.
abstract: OBJECTIVE
  Methylmalonic aciduria is the most common organic aciduria in mainland China. Succinate-CoA ligase deficiency causes encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Patients usually present with severe encephalomyopathy, infantile lactic acidosis, which can be fatal, and mild methylmalonic aciduria.
  
  
  METHODS
  Three Chinese patients (two boys and one girl) were hospitalized because of severe encephalomyopathy between 7 and 9 months. They presented with severe psychomotor retardation, hypotonia, dystonia, athetoid movements, seizures, feeding problems and failure to thrive. Mild elevated urine methylmalonic acid and blood propionylcarnitine indicated methylmalonic aciduria. Gene capture and high-throughput genomic sequencing was carried out.
  
  
  RESULTS
  Five novel mutations in SUCLG1 were identified in these patients: c.550G>A (p.G184S) in exon 5, c.751C>T (p.G251S) in exon 7, c.809A>C (p.L270W) in exon 7, c.961C>G (p.A321P) in exon 8 and c.826-2A>G (Splicing) in exon 9. Significant depletion of mtDNA was not observed in the peripheral leukocytes of the three patients in spite of mild decreasing of mitochondrial respiratory chain complex I in two patients and complex V in one patient. After treatment with cobalamin, calcium folinate, L-carnitine, vitamin B1, C, and coenzyme Q10, and nutrition intervention, the patients improved.
  
  
  CONCLUSIONS
  Succinate-CoA ligase deficiency due to SUCLG1 mutations is a rare cause of methylmalonic aciduria. Biochemical and gene studies are keys for the differential diagnoses. Three Chinese patients with mild methylmalonic aciduria were genetically diagnosed using high-throughput genomic sequencing. Five novel pathogenic mutations in SUCLG1 were identified.
authors.affiliation: Peking University First Hospital, Beijing 100034, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Peking University First Hospital, Beijing 100034, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Peking University First Hospital, Beijing 100034, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Peking University First Hospital, Beijing 100034, China.
authors.forename: Jinqing
authors.initials: J
authors.lastname: Song
authors.affiliation: Peking University First Hospital, Beijing 100034, China. Electronic address: organic.acid@126.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013389:Succinate-CoA Ligases / Q000235:genetics*
chemical_list: C000611245:SUCLG1 protein, human; D013389:Succinate-CoA Ligases
keywords: Encephalomyopathy; Methylmalonic aciduria; Mitochondrial DNA depletion; SUCLG1; Succinate-CoA ligase deficiency