E Huishu, Han Lianshu, Ye Jun, Qiu Wenjuan, Zhang Huiwen, Liang Lili, Wang Yu, Wang Jianguo, Ji Wenjun, Chen Ting, Xu Feng, Gu Xuefan
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Feb 10;37(2):101-105. doi: 10.3760/cma.j.issn.1003-9406.2020.02.001.
To explore the clinical feature, genetic variant and clinical outcome of patients with cblA-type methylmalonic acidemia (MMA).
Clinical manifestations, therapeutic schedule and prognosis of 12 patients with cblA type MMA were analyzed. MMAA gene variants were analyzed for all patients and their parents.
Vomiting, dyspnea and drowsiness were the major clinical features of cblA-type MMA. Eleven patients were vitamin B12-responsive. After treatment, the blood level of propionylcarnitine, ratio of propionylcarnitine/acetylcarnitine, urine level of methylmalonic acid and methylcitric acid have decreased significantly (P< 0.05). Follow-up study showed that 8 patients (66.7%) had normal development, while the rest (33.3%) remained to have various level of mental or movement delay. Fourteen MMAA gene variants were detected, with c.365T>C (p.L122P) being the most common (29.2%). Six novel variants, including c.54delA (p.A19Hfs43), c.275G>A (p.G92V), c.456delT (p.G153Vfs8), c.667dupA (p.T223Nfs4), c.1114C>T (p.Q372X) and c.1137_1138delCA (p.F379Lfs27) were found.
The main clinical manifestations of patients with cblA-type of MMA include vomiting, dyspnea and drowsiness. Most patients are vitamin B12-responsive. c.365T>C is a potential hot spot variant of MMAA gene in China.
探讨cblA 型甲基丙二酸血症（MMA）患者的临床特征、基因变异及临床结局。
分析12例cblA 型MMA患者的临床表现、治疗方案及预后。对所有患者及其父母进行MMAA基因变异分析。
呕吐、呼吸困难和嗜睡是cblA 型MMA的主要临床特征。11例患者对维生素B12有反应。治疗后，丙酰肉碱血水平、丙酰肉碱/乙酰肉碱比值、甲基丙二酸和甲基柠檬酸尿水平均显著下降（P<0.05）。随访研究显示，8例患者（66.7%）发育正常，其余患者（33.3%）仍有不同程度的智力或运动发育迟缓。共检测到14种MMAA基因变异，其中c.365T>C（p.L122P）最为常见（29.2%）。发现6种新变异，包括c.54delA（p.A19Hfs43）、c.275G>A（p.G92V）、c.456delT（p.G153Vfs8）、c.667dupA（p.T223Nfs4）、c.1114C>T（p.Q372X）和c.1137_1138delCA（p.F379Lfs27）。
cblA 型MMA患者的主要临床表现包括呕吐、呼吸困难和嗜睡。大多数患者对维生素B12有反应。c.365T>C是中国MMAA基因的一个潜在热点变异。
