Mutation Profile of the MUT Gene in Chinese Methylmalonic Aciduria Patients

Liu, Mei Ying; Liu, Tze Tze; Yang, Yang Ling; Chang, Ying Chen; Fan, Ya Ling; Lee, Shu Fen; Teng, Yu Ting; Chiang, Szu Hui; Niu, Dau Ming; Lin, Shio Jean; Chao, Mei Chun; Lin, Shuan Pei; Han, Lian Shu; Qi, Yu; Hsiao, Kwang Jen

doi:10.1007/8904_2011_117

Cited by 23 publications

(11 citation statements)

References 22 publications

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“…Thus, the common genotypes appear to vary geographically around the world. The allele frequency of c.729_730insTT has been reported in two groups of Chinese patients (15.4% and 10.7%), compared with the 14.2% in our cohort, indicating a similar frequency among different groups of Chinese patients. However, c.729_730insTT was identified in 4 alleles in 151 European patients (1.3%), which was far lower than that in the Chinese population.…”

Section: Discussionsupporting

confidence: 72%

A study on a cohort of 301 Chinese patients with isolated methylmalonic acidemia

Kang

Liu

Shen

et al. 2019

J of Inher Metab Disea

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Methylmalonic acidemia (MMA) is the most common organic acidemia in China. This study aimed to characterise the genotypic and phenotypic variabilities, and the molecular epidemiology of Chinese patients with isolated MMA. Patients (n = 301) with isolated MMA were diagnosed by clinical examination, biochemical assays, and genetic analysis. Fifty-eight patients (19.3%) were detected by newborn screening and 243 patients (80.7%) were clinically diagnosed after onset. Clinical onset ranged from the age of 3 days to 23 years (mean age = 1.01 ± 0.15 years). Among 234 MMA patients whose detailed clinical data were available, 170 (72.6%) had early onset disease (before the age of 1 year), and 64 (27.4%) had late-onset disease. The 234 MMA patients manifested with neuropsychiatric impairment (65.4%), haematological abnormality (31.6%), renal damage (8.5%), and metabolic crises (67.1%). Haematological abnormality was significantly more common in early-onset patients than that in late-onset patients. The incidence of metabolic crises was significantly high (P < 0.001) in patients with mut type than those with other types of isolated MMA. Variations (n = 122) were identified in MMUT, MMAA, MMAB, MMADHC, SUCLG1, and SUCLA2, of which 45 were novel. c.729_730insTT was the most frequent MMUT mutation, with a significantly higher frequency in our patients than that in 151 reported European patients. The frequency of c.914T>C in MMUT in our cohort was also higher than that in 151 European patients. MMUT mutations

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Section: Discussionsupporting

confidence: 72%

A study on a cohort of 301 Chinese patients with isolated methylmalonic acidemia

Kang

Liu

Shen

et al. 2019

J of Inher Metab Disea

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“…The genotypes of Taiwanese patients appear to differ from the People’s Republic of China, where the most common defect (12 out of 78 mutant alleles, 15%) is c.729_730insTT (p.D244Lfs*39) [24], which only occurred once out of 56 mutants alleles (1.8%) from our data in Taiwan. On the contrary, the genotypes in Taiwan appear similar to Southern part of China, where the leading mutant allele is G427D, followed by c.1630_1631GG > TA (p.G544X) [25] Our findings also differ from those of Japan, where the most frequent mutations are p.E117X, c.385 + 5G > A, p.R369H, p.L494X, and p.R727X [26]. We also found that 17 (81%) patients were classified as mut 0 .…”

Section: Discussionmentioning

confidence: 99%

Methylmalonic acidemia/propionic acidemia – the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups

Chu

Chien

Lin

et al. 2019

Orphanet J Rare Dis

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Background Most patients with isolated methylmalonic acidemia (MMA) /propionic acidemia (PA) presenting during the neonatal period with acute metabolic distress are at risk for death and significant neurodevelopmental disability. The nationwide newborn screening for MMA/PA has been in place in Taiwan from January, 2000 and data was collected until December, 2016. Results During the study period, 3,155,263 newborns were screened. The overall incidence of MMA mutase type cases was 1/121,356 ( n = 26), 1 cobalamin B was detected and that for PA cases ( n = 4) was 1/788,816. The time of referral is 8.8 days for MMA patients, and 7.5 days for PA patients. The MMA mutase type patients have higher AST, ALT, and NH 3 values as well as a lower pH value ( p < 0.05). The mean age for liver transplantation (LT) is 402 days (range from 0.6–6.7 yr) with 16 out of 20 cases (80.0%) using living donors. The mean admission length shortened from 90.6 days/year (pre-LT) to 5.3 days/year (at 3rd year post-LT) ( p < 0.0005). Similarly, the tube feeding ratio decreased from 67.8 to 0.50% ( p < 0.00005). The anxiety level of the caregiver was reduced from 33.4 to 27.2 after LT ( p = 0.001) and the DQ/IQ performance of the patients was improved after LT from 50 to 60.1 ( p = 0.07). Conclusion MMA/PA patients with LT do survive and have reduced admission time, reduced tube feeding and the caregiver is less anxious.

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“…The patients were diagnosed biochemically and genetically (patient 1, genetic analysis was not available; patient 2, c.323G>A (p.R108H)/ c.729_730insTT; patient 3, c.1560+1 G>T/c.2075 T>C (p.L692P); patient 4, c.683G>A (p.R228Q)/c.1106G>A (p.R369H)). Several of these mutations have been reported previously as pathogenic mutations [15][16][17][18].…”

Section: Patients and Healthy Individualsmentioning

confidence: 95%

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry

et al. 2015

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Methylmalonic acidemia (MMA) is an inherited metabolic disease. In this condition, metabolism from methylmalonyl coenzyme A (CoA) to succinyl-CoA is inhibited because of either low methylmalonyl-CoA mutase (MCM) activity or adenosylcobalamin deficiency owing to altered vitamin B12 metabolism. A high-precision assay for detecting MCM activity would facilitate not only MMA diagnosis but also the ability to determine the severity of MMA. We developed an MCM assay method based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) that involves the determination of succinyl-CoA, which is formed in an enzyme reaction, using peripheral lymphocytes. Using 0.05, 0.5, and 5 μmol/L succinyl-CoA, the intra-assay coefficient of variation (CV) was less than 5.2% and the inter-assay CV was less than 8.7%. The MCM activities of five healthy individuals and four patients were investigated with this assay. The MCM activities of the patients were very low in relation to those of healthy individuals. Together, these results show that the UPLC-MS/MS method is useful for a detailed MCM activity assay.

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Mutation Profile of the MUT Gene in Chinese Methylmalonic Aciduria Patients

Cited by 23 publications

References 22 publications

A study on a cohort of 301 Chinese patients with isolated methylmalonic acidemia

A study on a cohort of 301 Chinese patients with isolated methylmalonic acidemia

Methylmalonic acidemia/propionic acidemia – the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry

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