The Follow-Up of Chinese Patients in cblC Type Methylmalonic Acidemia Identified Through Expanded Newborn Screening

• Published in: Frontiers in genetics Vol. 13; p. 805599
• Main Authors: Ling, Shiying, Wu, Shengnan, Shuai, Ruixue, Yu, Yue, Qiu, Wenjuan, Wei, Haiyan, Yang, Chiju, Xu, Peng, Zou, Hui, Feng, Jizhen, Niu, Tingting, Hu, Haili, Zhang, Huiwen, Liang, Lili, Lu, Deyun, Gong, Zhuwen, Zhan, Xia, Ji, Wenjun, Gu, Xuefan, Han, Lianshu
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 15.02.2022
• Subjects: Genetics; long-term outcome; methylmalonic acidemia combined with homocysteinemia; MMACHC gene; newborn screening; tandem mass spectrometry; MMACHC gene; long-term outcome; tandem mass spectrometry; newborn screening; methylmalonic acidemia combined with homocysteinemia
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2022.805599

The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual. A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. We collected a large cohort of 538 patients and investigated their clinical data in detail, including disease onset, biochemical metabolites, and gene variation, and explored different factors on the prognosis. The long-term outcomes of all patients were evaluated, representing 44.6% for poor outcomes. In our comparison of patients with already occurring clinical signs before treatment to asymptomatic ones, the incidence of intellectual impairment, movement disorders, ocular complications, hydrocephalus, and death were significantly different ( < 0.01). The presence of disease onset [Odd ratio (OR) 12.39, 95% CI 5.15-29.81; = 0.000], variants of c.609G>A (OR 2.55, 95% CI 1.49-4.35; = 0.001), and c.567dupT (OR 2.28, 95% CI 1.03-5.05; = 0.042) were independently associated with poor outcomes, especially for neurodevelopmental deterioration. NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have protective effects on the prognosis of infants with cblC defect.