E Huishu, Han Lianshu, Ye Jun, Qiu Wenjuan, Zhang Huiwen, Liang Lili, Wang Yu, Wang Jianguo, Ji Wenjun, Chen Ting, Xu Feng, Gu Xuefan
Abstract
ObjectiveTo explore the clinical feature, genetic variant and clinical outcome of patients with cblA-type methylmalonic acidemia (MMA).
MethodsClinical 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.
ResultsVomiting, 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. FourteenMMAA gene variants were detected, with c. 365T>C (p.L122P) being the most common (29.2%). Six novel variants, including c. 54delA (p.A19Hfs*43), c. 275G>A (p.G92V), c. 456delT (p.G153Vfs*8), c. 667dupA (p.T223Nfs*4), c. 1114C>T (p.Q372X) and c. 1137_1138delCA (p.F379Lfs*27) were found.
ConclusionThe 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 ofMMAA gene in China.
Key words:
Methylmalonic acidemia; MMAA gene; Propionylcarnitine; Methylmalonic acid
Contributor Information
E Huishu
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Han Lianshu
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Ye Jun
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Qiu Wenjuan
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Zhang Huiwen
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Liang Lili
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Wang Yu
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Wang Jianguo
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Ji Wenjun
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Chen Ting
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Xu Feng
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
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
