Late-onset cblC defect: clinical, biochemical and molecular analysis
Abstract Background cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with...
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| Format: | Article |
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BMC
2023-09-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02890-4 |
| _version_ | 1827708386243772416 |
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| author | Si Ding Shiying Ling Lili Liang Wenjuan Qiu Huiwen Zhang Ting Chen Xia Zhan Feng Xu Xuefan Gu Lianshu Han |
| author_facet | Si Ding Shiying Ling Lili Liang Wenjuan Qiu Huiwen Zhang Ting Chen Xia Zhan Feng Xu Xuefan Gu Lianshu Han |
| author_sort | Si Ding |
| collection | DOAJ |
| description | Abstract Background cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with late-onset cblC defect. Methods A total of 85 patients with late-onset cblC defect were enrolled. Clinical data, including manifestations, metabolites, molecular diagnosis, treatment and outcome, were summarized and analyzed. Results The age of onset ranged from 2 to 32.8 years old (median age 8.6 years, mean age 9.4 years). The time between first symptoms and diagnosis ranged from a few days to 20 years (median time 2 months, mean time 20.7 months). Neuropsychiatric symptoms were presented as first symptoms in 68.2% of cases, which were observed frequently in schoolchildren or adolescents. Renal involvement and cardiovascular disease were observed in 20% and 8.2% of cases, respectively, which occurred with the highest prevalence in preschool children. Besides the initial symptoms, the disease progressed in most patients and cognitive decline became the most frequent symptom overall. The levels of propionylcarnitine, propionylcarnitine / acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine, were decreased remarkably after treatment (P<0.001). Twenty-four different mutations of MMACHC were identified in 78 patients, two of which were novel. The c.482G>A variant was the most frequent mutated allele in this cohort (25%). Except for 16 patients who recovered completely, the remaining patients were still left with varying degrees of sequelae in a long-term follow-up. The available data from 76 cases were analyzed by univariate analysis and multivariate logistic regression analysis, and the results showed that the time from onset to diagnosis (OR = 1.025, P = 0. 024) was independent risk factors for poor outcomes. Conclusions The diagnosis of late-onset cblC defect is often delayed due to poor awareness of its various and nonspecific symptoms, thus having an adverse effect on the prognosis. It should be considered in patients with unexplained neuropsychiatric and other conditions such as renal involvement, cardiovascular diseases or even multiple organ damage. The c.482G>A variant shows the highest frequency in these patients. Prompt treatment appears to be beneficial. |
| first_indexed | 2024-03-10T17:02:51Z |
| format | Article |
| id | doaj.art-75b7f9c5de2e49f1b905e55958015cca |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-10T17:02:51Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-75b7f9c5de2e49f1b905e55958015cca2023-11-20T10:54:16ZengBMCOrphanet Journal of Rare Diseases1750-11722023-09-011811910.1186/s13023-023-02890-4Late-onset cblC defect: clinical, biochemical and molecular analysisSi Ding0Shiying Ling1Lili Liang2Wenjuan Qiu3Huiwen Zhang4Ting Chen5Xia Zhan6Feng Xu7Xuefan Gu8Lianshu Han9Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of MedicineAbstract Background cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with late-onset cblC defect. Methods A total of 85 patients with late-onset cblC defect were enrolled. Clinical data, including manifestations, metabolites, molecular diagnosis, treatment and outcome, were summarized and analyzed. Results The age of onset ranged from 2 to 32.8 years old (median age 8.6 years, mean age 9.4 years). The time between first symptoms and diagnosis ranged from a few days to 20 years (median time 2 months, mean time 20.7 months). Neuropsychiatric symptoms were presented as first symptoms in 68.2% of cases, which were observed frequently in schoolchildren or adolescents. Renal involvement and cardiovascular disease were observed in 20% and 8.2% of cases, respectively, which occurred with the highest prevalence in preschool children. Besides the initial symptoms, the disease progressed in most patients and cognitive decline became the most frequent symptom overall. The levels of propionylcarnitine, propionylcarnitine / acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine, were decreased remarkably after treatment (P<0.001). Twenty-four different mutations of MMACHC were identified in 78 patients, two of which were novel. The c.482G>A variant was the most frequent mutated allele in this cohort (25%). Except for 16 patients who recovered completely, the remaining patients were still left with varying degrees of sequelae in a long-term follow-up. The available data from 76 cases were analyzed by univariate analysis and multivariate logistic regression analysis, and the results showed that the time from onset to diagnosis (OR = 1.025, P = 0. 024) was independent risk factors for poor outcomes. Conclusions The diagnosis of late-onset cblC defect is often delayed due to poor awareness of its various and nonspecific symptoms, thus having an adverse effect on the prognosis. It should be considered in patients with unexplained neuropsychiatric and other conditions such as renal involvement, cardiovascular diseases or even multiple organ damage. The c.482G>A variant shows the highest frequency in these patients. Prompt treatment appears to be beneficial.https://doi.org/10.1186/s13023-023-02890-4cblC defectLate-onsetMethylmalonic acidemia and homocystinuriaNeuropsychiatric symptomsPrognosis |
| spellingShingle | Si Ding Shiying Ling Lili Liang Wenjuan Qiu Huiwen Zhang Ting Chen Xia Zhan Feng Xu Xuefan Gu Lianshu Han Late-onset cblC defect: clinical, biochemical and molecular analysis Orphanet Journal of Rare Diseases cblC defect Late-onset Methylmalonic acidemia and homocystinuria Neuropsychiatric symptoms Prognosis |
| title | Late-onset cblC defect: clinical, biochemical and molecular analysis |
| title_full | Late-onset cblC defect: clinical, biochemical and molecular analysis |
| title_fullStr | Late-onset cblC defect: clinical, biochemical and molecular analysis |
| title_full_unstemmed | Late-onset cblC defect: clinical, biochemical and molecular analysis |
| title_short | Late-onset cblC defect: clinical, biochemical and molecular analysis |
| title_sort | late onset cblc defect clinical biochemical and molecular analysis |
| topic | cblC defect Late-onset Methylmalonic acidemia and homocystinuria Neuropsychiatric symptoms Prognosis |
| url | https://doi.org/10.1186/s13023-023-02890-4 |
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