Clinical and Genetic Characteristics of Mitochondrial DNA Depletion Syndrome Associated with SUCLG1 Variants in China.

Abstract

This study aimed to summarize the genetic variants and clinical characteristics of mitochondrial DNA depletion syndrome (MDS) associated with SUCLG1 mutations in children from China. A systematic review of cases reported in a Chinese literature database was conducted. Clinical data and genetic findings of children with MDS caused by SUCLG1 mutations were analyzed. A total of 13 cases from 9 articles were identified. The primary clinical features included hypotonia, psychomotor retardation, feeding difficulties, growth retardation, hearing impairment, and liver function impairment. Urine organic acid analysis demonstrated a mild increase in methylmalonic acid, while plasma concentrations of propionylcarnitine and/or butyrylcarnitine were elevated. Additionally, increased lactate and pyruvic acid levels were observed in both plasma and cerebrospinal fluid. Brain magnetic resonance imaging identified basal ganglion lesions and/or cerebral atrophy. A total of 14 SUCLG1 variants were identified: c.550G>A, c.751C>T, c.809A>C, c.961C>G, c.826-2A>G, c.713T>C, c.916G>T, c.619T>C, c.980dupT, c.40A>G, c.142C>T, c.601A>G, c.871G>C, and c.721_c.722delGA. Among these, the c.826-2A>G variation was the most frequently detected, present in 4 children, followed by c.550G>A. No significant correlation was found between genotype and phenotype. All 13 children were treated with vitamin B complex and coenzyme Q10. Among them, 2 died, while the remaining children exhibited clinical improvement. MDS associated with SUCLG1 mutations presents with nonspecific clinical manifestations and can affect multiple organ systems. Genetic testing is necessary for diagnosis, and no definitive treatment is currently available.