Phenotypes and genotypes of 78 patients with propionic acidemia.
10.3760/cma.j.cn112150-20220620-00630
- Author:
Xue MA
1
;
Yi LIU
2
;
Zhe Hui CHEN
1
;
Yao ZHANG
1
;
Hui DONG
1
;
Jin Qing SONG
1
;
Ying JIN
1
;
Meng Qiu LI
1
;
Lu Lu KANG
3
;
Ru Xuan HE
4
;
Yuan DING
5
;
Dong Xiao LI
6
;
Hong ZHENG
7
;
Li Ying SUN
8
;
Zhi Jun ZHU
8
;
Yan Ling YANG
1
;
Yongtong CAO
2
Author Information
1. Department of Pediatrics, Peking University First Hospital, Beijing 100034,China.
2. Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029,China.
3. Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
4. Department of Respiratory, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
5. Department of Endocrinology and Genetic, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
6. Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated of Zhengzhou University, Zhengzhou 450053, China.
7. Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450099, China.
8. Department of General Surgery, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.
- Publication Type:Observational Study
- MeSH:
Carnitine;
Female;
Genotype;
Humans;
Male;
Methylmalonyl-CoA Decarboxylase/metabolism*;
Mutation;
Phenotype;
Propionic Acidemia/genetics*;
Retrospective Studies
- From:
Chinese Journal of Preventive Medicine
2022;56(9):1263-1271
- CountryChina
- Language:Chinese
-
Abstract:
Objective: Propionic acidemia is a rare inherited metabolic disorder caused by propionyl CoA carboxylase (PCC) deficiency. This study aims to analyze the clinical characteristics and gene variations of Chinese patients with propionic acidemia, and to explore the correlation between clinical phenotypes and genotypes. Methods: Single-center, retrospective and observational study. Seventy-eight patients of propionic acidemia (46 males and 32 females) from 20 provinces and autonomous regions were admitted from January 2007 to April 2022. Their age of initial diagnosis ranged from 7 days to 15 years. The clinical manifestations, biochemical and metabolic abnormalities, genetic variations, diagnosis, treatment and outcome were studied. Chi-Square test or Mann-Whitney U test were used for statistical analysis. Results: Among 78 cases, 6 (7.7%) were identified by newborn screening; 72 (92.3%) were clinically diagnosed after onset, and the age of onset was 2 hours after birth to 15 years old; 32 cases had early-onset disease and 40 cases had late-onset disease. The initial manifestations included lethargy, hypotonia, vomiting, feeding difficulties, developmental delay, epilepsy, and coma. Among the 74 cases who accepted gene analysis, 35 (47.3%) had PCCA variants and 39 (52.7%) had PCCB variants. A total of 39 PCCA variants and 32 PCCB variants were detected, among which c.2002G>A and c.229C>T in PCCA and c.838dupC and c.1087T>C in PCCB were the most common variants in this cohort. The variants c.1228C>T and c.1283C>T in PCCB may be related to early-onset type. The variants c.838dupC, c.1127G>T and c.1316A>G in PCCB, and c.2002G>A in PCCA may be related to late-onset disease. Six patients detected by newborn screening and treated at asymptomatic stage developed normal. The clinically diagnosed 72 cases had varied complications. 10 (12.8%) cases of them died. 62 patients improved after metabolic therapy by L-carnitine and diet. Six patients received liver transplantation because of recurrent metabolic crisis. Their clinical symptoms were markedly improved. Conclusion: The clinical manifestations of propionic acidemia are complex and lack of specificity. Newborn screening and high-risk screening are keys for early treatment and better outcome. The correlation between the genotype and phenotype of propionic acidemia is unclear, but certain variants may be associated with early-onset or late-onset propionic acidemia.
