Late-onset cblC defect: clinical, biochemical and molecular analysis

作者：Si Ding, Shiying Ling, Lili Liang, Wenjuan Qiu, Huiwen Zhang, Ting Chen, Xia Zhan, Feng Xu, Xuefan Gu, Lianshu Han · 发表于：Orphanet Journal of Rare Diseases · 年份：2023 · DOI：10.1186/s13023-023-02890-4 · 被引用次数：12 · 研究领域：Metabolism and Genetic Disorders、Folate and B Vitamins Research、Diet and metabolism studies

BACKGROUND: cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with late-onset cblC defect. METHODS: A total of 85 patients with late-onset cblC defect were enrolled. Clinical data, including manifestations, metabolites, molecular diagnosis, treatment and outcome, were summarized and analyzed. RESULTS: The age of onset ranged from 2 to 32.8 years old (median age 8.6 years, mean age 9.4 years). The time between first symptoms and diagnosis ranged from a few days to 20 years (median time 2 months, mean time 20.7 months). Neuropsychiatric symptoms were presented as first symptoms in 68.2% of cases, which were observed frequently in schoolchildren or adolescents. Renal involvement and cardiovascular disease were observed in 20% and 8.2% of cases, respectively, which occurred with the highest prevalence in preschool children. Besides the initial symptoms, the disease progressed in most patients and cognitive decline became the most frequent symptom overall. The levels of propionylcarnitine, propionylcarnitine / acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine, were decreased remarkably after treatment (P<0.001). Twenty-four different mutations of MMACHC were identified in 78 patients, two of which were novel. The c.482G>A variant was t...