Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment

• Published in: Orphanet journal of rare diseases Vol. 17; no. 1; pp. 1 - 330
• Main Authors: Chen, Zhehui, Dong, Hui, Liu, Yupeng, He, Ruxuan, Song, Jinqing, Jin, Ying, Li, Mengqiu, Liu, Yi, Liu, Xueqin, Yan, Hui, Qi, Jianguang, Wang, Fang, Xiao, Huijie, Zheng, Hong, Kang, Lulu, Li, Dongxiao, Zhang, Yao, Yang, Yanling
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 02.09.2022; BioMed Central; BMC
• Subjects: Aciduria; Adolescence; Age; Behavior disorders; Betaine; Blindness; Cardiovascular diseases; Care and treatment; Carnitine; cblC; Child development; Complications and side effects; Creatinine; Diagnosis; Disease; Encephalitis; Females; Genetic analysis; Genetic diversity; Genetic screening; Health aspects; Hereditary spastic paraplegia; Infections; Medical diagnosis; Medical research; Medical screening; Mental disorders; Metabolism; Methylmalonic aciduria; Middle schools; Movement disorders; Multiple organ damage; Neuropsychiatric symptoms; Paralysis; Patients; Psychosis; Puberty; Pulmonary hypertension; Rare diseases; Teenagers; Vitamin B12; Vitamin D; Vitamin deficiency; China
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-022-02471-x

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. 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.