单位：[1]Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.[2]Department of Pediatrics, Peking University People’s Hospital, Beijing 100034, China.[3]Department of Respiratory Medicine II, Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, China.首都医科大学附属北京儿童医院[4]Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China.[5]Department of Pediatrics, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000,China.[6]Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.[7]Henan Key Laboratory of Children’s Genetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China.
Background cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. Results This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, l-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. Conclusions Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, l-carnitine, and betaine appears to be beneficial.
基金：
This work was supported by grants from the National Key Research and Development
Program of China (Nos. 2019YFC1005100, 2017YFC1001700).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|2 区医学
小类|3 区遗传学3 区医学：研究与实验
最新[2025]版：
大类|2 区医学
小类|2 区遗传学2 区医学：研究与实验
JCR分区：
出版当年[2020]版：
Q2GENETICS & HEREDITYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q2GENETICS & HEREDITYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
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推荐引用方式(GB/T 7714)：
Chen Zhehui,Dong Hui,Liu Yupeng,et al.Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment[J].ORPHANET JOURNAL OF RARE DISEASES.2022,17(1):doi:10.1186/s13023-022-02471-x.
APA：
Chen, Zhehui,Dong, Hui,Liu, Yupeng,He, Ruxuan,Song, Jinqing...&Yang, Yanling.(2022).Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment.ORPHANET JOURNAL OF RARE DISEASES,17,(1)
MLA：
Chen, Zhehui,et al."Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment".ORPHANET JOURNAL OF RARE DISEASES 17..1(2022)
