甲基丙二酸血症
甲基丙二酸
基因型
医学
内科学
甲基丙二酸尿症
胃肠病学
复合杂合度
新生儿筛查
疾病
表型
儿科
遗传学
基因
生物
同型半胱氨酸
作者
Lili Liang,Shiying Ling,Yue Yu,Ruixue Shuai,Wenjuan Qiu,Huiwen Zhang,Linghua Shen,Shengnan Wu,Haiyan Wei,Yongxing Chen,Chiju Yang,Peng Xu,Xigui Chen,Hui Zou,Jizhen Feng,Tingting Niu,Haili Hu,Zhuwen Gong,Ting Chen,Xia Zhan,Xuefan Gu,Lianshu Han
标识
DOI:10.1136/jmg-2022-108682
摘要
Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut-type MMA in Chinese patients.We recruited 365 patients with mut-type MMA; investigated their disease onset, newborn screening (NBS) status, biochemical metabolite levels, gene variations and prognosis; and explored the relationship between phenotype and genotype.There were 152 patients diagnosed by tandem mass spectrometry (MS/MS) expanded NBS, 209 patients diagnosed because of disease onset without NBS and 4 cases diagnosed because of sibling diagnosis. The median age of onset was 15 days old, with a variety of symptoms without specificity. Urinary levels of methylmalonic acid and methylcitric acid (MCA) decreased after treatment. Regarding the prognosis, among the 152 patients with NBS, 50.6% were healthy, 30.3% had neurocognitive impairment and/or movement disorders and 13.8% died. Among the 209 patients without NBS, 15.3% were healthy, 45.9% had neurocognitive impairment and/or movement disorders and 33.0% died. In total, 179 variants were detected in the MMUT gene, including 52 novel variations. c.729_730insTT, c.1106G>A, c.323G>A, c.914T>C and c.1663G>A were the five most frequent variations. The c.1663G>A variation led to a milder phenotype and better prognosis.There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis.
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