Study on Inherited Endocrine and Metabolic Disease
Heterogeneous phenotypes, genotypes, treatment and prevention of 1 003 patients with methylmalonic acidemia in the mainland of China
Yi Liu, Yupeng Liu, Yao Zhang, Jinqing Song, Hong Zheng, Hui Dong, Yanyan Ma, Tongfei Wu, Qiao Wang, Xiyuan Li, Yuan Ding, Dongxiao Li, Ying Jin, Mengqiu Li, Zhaoxia Wang, Yun Yuan, Haixia Li, Jiong Qin, Yanling Yang
Published 2018-06-02
Cite as Chin J Pediatr, 2018, 56(6): 414-420. DOI: 10.3760/cma.j.issn.0578-1310.2018.06.003
Abstract
ObjectiveTo analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated.
MethodsTottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families.
ResultsAmong 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis.
ConclusionCombined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.
Key words:
Inherited metabolic disorders; Methylmalonic acidemia; Homocysteinemia; Neonatal screening; Prenatal diagnosis
Contributor Information
Yi Liu
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
Yupeng Liu
Department of Pediatrics, Peking University People's Hospital, Beijing 100044, China
Yao Zhang
Jinqing Song
Hong Zheng
Hui Dong
Yanyan Ma
Tongfei Wu
Qiao Wang
Xiyuan Li
Yuan Ding
Dongxiao Li
Ying Jin
Mengqiu Li
Zhaoxia Wang
Yun Yuan
Haixia Li
Jiong Qin
Yanling Yang