The phenotypes and genotypes in 314 patients with isolated methylmalonic acidemia

The phenotypes and genotypes in 314 patients with isolated methylmalonic acidemia

Objectives: To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention. Methods: Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemi...

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Veröffentlicht in:Zhonghua er ke za zhi = Chinese journal of pediatrics. - 1960. - 58(2020), 6 vom: 02. Juni, Seite 468-475
1. Verfasser: Kang, L L (VerfasserIn)
Weitere Verfasser: Liu, Y P, Shen, M, Chen, Z H, Song, J Q, He, R X, Liu, Y, Zhang, Y, Dong, H, Li, M Q, Jin, Y, Zheng, H, Wang, Q, Ding, Y, Li, X Y, Li, D X, Li, H X, Liu, X Q, Xiao, H J, Jiang, Y W, Xiong, H, Zhang, C Y, Wang, Z X, Yuan, Y, Liang, D S, Tian, Y P, Yang, Y L
Format: Online-Aufsatz
Sprache:Chinese
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Zhonghua er ke za zhi = Chinese journal of pediatrics
Schlagworte:Journal Article Methylmalonic acid Methylmalonyl-CoA mutase Newborn screening Tandem mass spectrometry Methylmalonic Acid 8LL8S712J7
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245 1 4 |a The phenotypes and genotypes in 314 patients with isolated methylmalonic acidemia 
264 1 |c 2020 
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500 |a Date Completed 10.09.2020 
500 |a Date Revised 07.12.2022 
500 |a published: Print 
500 |a Citation Status MEDLINE 
520 |a Objectives: To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention. Methods: Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test. Results: Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ(2)=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common (n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ(2)=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ(2)=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ(2)=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions: The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects 
650 4 |a Journal Article 
650 4 |a Methylmalonic acid 
650 4 |a Methylmalonyl-CoA mutase 
650 4 |a Newborn screening 
650 4 |a Tandem mass spectrometry 
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650 7 |a 8LL8S712J7  |2 NLM 
700 1 |a Liu, Y P  |e verfasserin  |4 aut 
700 1 |a Shen, M  |e verfasserin  |4 aut 
700 1 |a Chen, Z H  |e verfasserin  |4 aut 
700 1 |a Song, J Q  |e verfasserin  |4 aut 
700 1 |a He, R X  |e verfasserin  |4 aut 
700 1 |a Liu, Y  |e verfasserin  |4 aut 
700 1 |a Zhang, Y  |e verfasserin  |4 aut 
700 1 |a Dong, H  |e verfasserin  |4 aut 
700 1 |a Li, M Q  |e verfasserin  |4 aut 
700 1 |a Jin, Y  |e verfasserin  |4 aut 
700 1 |a Zheng, H  |e verfasserin  |4 aut 
700 1 |a Wang, Q  |e verfasserin  |4 aut 
700 1 |a Ding, Y  |e verfasserin  |4 aut 
700 1 |a Li, X Y  |e verfasserin  |4 aut 
700 1 |a Li, D X  |e verfasserin  |4 aut 
700 1 |a Li, H X  |e verfasserin  |4 aut 
700 1 |a Liu, X Q  |e verfasserin  |4 aut 
700 1 |a Xiao, H J  |e verfasserin  |4 aut 
700 1 |a Jiang, Y W  |e verfasserin  |4 aut 
700 1 |a Xiong, H  |e verfasserin  |4 aut 
700 1 |a Zhang, C Y  |e verfasserin  |4 aut 
700 1 |a Wang, Z X  |e verfasserin  |4 aut 
700 1 |a Yuan, Y  |e verfasserin  |4 aut 
700 1 |a Liang, D S  |e verfasserin  |4 aut 
700 1 |a Tian, Y P  |e verfasserin  |4 aut 
700 1 |a Yang, Y L  |e verfasserin  |4 aut 
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856 4 0 |u http://dx.doi.org/10.3760/cma.j.cn112140-20200401-00339  |3 Volltext 
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