Factors affecting phenotypes in the patients with MMACHC gene c. 609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria
10.3760/cma.j.cn511374-20210211-00130
- VernacularTitle:MMACHC c．609G>A纯合变异cblC型甲基丙二酸血症合并同型半胱氨酸尿症患者的表型差异
- Author:
Ruxuan HE
1
;
Ruo MO
;
Yao ZHANG
;
Ming SHEN
;
Lulu KANG
;
Zhehui CHEN
;
Yi LIU
;
Jinqing SONG
;
Hongwu ZHANG
;
Hongxin YAO
;
Yupeng LIU
;
Hui DONG
;
Ying JIN
;
Mengqiu LI
;
Jiong QIN
;
Hong ZHENG
;
Yongxing CHEN
;
Haiyan WEI
;
Dongxiao LI
;
Xiyuan LI
;
Rongxiu ZHENG
;
Huifeng ZHANG
;
Min HUANG
;
Chunyan ZHANG
;
Yuwu JIANG
;
Desheng LIANG
;
Yaping TIAN
;
Yanling YANG
Author Information
1. 北京大学第一医院儿科，北京 100034
- Keywords:
Methylmalonic acidemia;
Homocysteinemia;
MMACHC gene;
cblC type;
c. 609 G>A homozygous variant
- From:
Chinese Journal of Medical Genetics
2022;39(6):565-570
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.
