Clinical analysis and outcome of patients with c. 482G >A variant of MMACHC gene in cblC type methylmalonic acidemia
10.3760/cma.j.issn.1000-6699.2019.07.008
- VernacularTitle:甲基丙二酸血症MMACHC基因c.482G>A突变患者临床资料及随访分析
- Author:
Huishu E
1
;
Lianshu HAN
;
Jun YE
;
Wenjuan QIU
;
Huiwen ZHANG
;
Lili LIANG
;
Yu WANG
;
Jianguo WANG
;
Wenjun JI
;
Ting CHEN
;
Xuefan GU
Author Information
1. 上海交通大学医学院附属新华医院
- Keywords:
Methylmalonic acidemia;
MMACHC gene;
Methylmalonic acid;
Propionylcarnitine
- From:
Chinese Journal of Endocrinology and Metabolism
2019;35(7):581-585
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the clinical manifestations, treatment and outcomes of patients with c. 482G>A ( p. R161Q ) variant of MMACHC gene in cblC type methylmalonic acidemia ( MMA ) . Methods The clinical manifestations, mass spectrometry results, genotypes, treatment and outcomes of 75 patients with cblC type MMAcarryingc.482G>A(p.R161Q)variantwereretrospectivelyanalyzed.Results Ofthe75patients,57(76％) were from newborn screening and one of them had an onset. Among the rest 18 unscreened patients, 2 were diagnosed after their full sisters' or brothers' diagnosis, the others were clinical patients. There were 17 clinical patients, with the medium age of onset 12 years old (10 days～26 years old). 12 late onset patients (70.6％) presented with poor academic performance, memory loss, poor expression, and decreased exercise capacity, while 5 early onset patients (29.4％) presented with convulsion and delay of development. All patients were vitamin B12-responsive. The levels of blood propionylcarnitine, the ratio of propionylcarnitine to acetylcarnitine, urinary methylmalonic acid and methyldecanoic acid, and plasma homocysteine were significantly decreased after treatment (P< 0.01). All patients diagnosed from newborn screening had normal development. However, only 3 clinical patients had a rather normal outcomes and the others remained different levels of intelligence and ( or ) motor dysfunction after treatment. Conclusion The c.482G>A ( p. R161Q) variant of MMACHC gene is associated with late onset cblC type MMA. Patients with this variant have a better response to hydroxycobalamin than other variants. The outcome of patients diagnosed from the newborn screening is good. When symptoms occur, the disability rate is often high. Therefore, newborn screening is a recommended method to prevent this disease.
