Variable phenotypes and outcomes associated with the MMACHC c.609G&gt;A homologous mutation: long term follow-up in a large cohort of cases

He, Ruxuan; Mo, Ran; Shen, Ming; Kang, Lulu; Song, Jinqing; Liu, Yi; Chen, Zhehui; Zhang, Hongwu; Yao, Hongxin; Liu, Yupeng; Zhang, Yao; Dong, Hui; Ying, Jianming; Li, Mengqiu; Qin, Jiong; Zheng, Hong; Chen, Yongxing; Li, Dongxiao; Wei, Haiyan; Li, Xiyuan; Zhang, Huifeng; Huang, Minyi; Zhang, Chunyan; Jiang, Yuwu; Tian, Yaping; Yang, Yanling

doi:10.1186/s13023-020-01485-7

Cited by 22 publications

(29 citation statements)

References 39 publications

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“…Outcomes of Chinese patients with homozygous c.609G > A MMACHC variant reported recently in several studies 15‐17 . In the largest study, neurodevelopmental outcomes were normal in 10 patients identified by NBS and treated from the age of 15 days 15 . The c.609G > A MMACHC variant was identified in five patients (either homozygous or compound heterozygous, one patient from the SX group and four patients from the NB group) in our study.…”

Section: Discussionsupporting

confidence: 51%

“…The pathogenic c.271dupA (p.Arg91Lysfs*14) variant is the most frequent variant in Caucasians, and is associated with an early disease onset (<1 year) 12 . Outcomes of Chinese patients with homozygous c.609G > A MMACHC variant reported recently in several studies 15‐17 . In the largest study, neurodevelopmental outcomes were normal in 10 patients identified by NBS and treated from the age of 15 days 15 .…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of patients with cobalamin C deficiency: A single center experience

et al. 2020

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Biallelic variants in MMACHC results in the combined methylmalonic aciduria and homocystinuria, called cobalamin (cbl) C (cblC) deficiency. We report 26 patients with cblC deficiency with their phenotypes, genotypes, biochemical parameters, and treatment outcomes, who were diagnosed and treated at our center. We divided all cblC patients into two groups: group 1: SX group: identified after manifestations of symptoms (n = 11) and group 2: NB group: identified during the asymptomatic period via newborn screening (NBS) or positive family history of cblC deficiency (n = 15). All patients in the SX group had global developmental delay and/or cognitive dysfunction at the time of the diagnosis and at the last assessment. Seizure, stroke, retinopathy, anemia, cerebral atrophy, and thin corpus callosum in brain magnetic resonance imaging (MRI) were common in patients in the SX group. Global developmental delay and cognitive dysfunction was present in nine patients in the NB group at the last assessment. Retinopathy, anemia, and cerebral atrophy and thin corpus callosum in brain MRI were less frequent. We report favorable outcomes in patients identified in the neonatal period and treated pre‐symptomatically. Identification of cblC deficiency by NBS is crucial to improve neurodevelopmental outcomes.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Outcomes of patients with cobalamin C deficiency: A single center experience

et al. 2020

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“…c.609G>A was the most common variant found in Chinese patients with early onset cblC de ciency [21][22] . The c.658_660delAAG mutation was the third and the c.567dupT mutation was the fourth most common mutations.…”

Section: Discussionmentioning

confidence: 97%

Easily Misdiagnosed cblC Deficiency in Adolescents: the Clinical and Metabolic Studies

Chen

Dong

Liu

et al. 2022

Preprint

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Purpose: Adolescents are easily attacked by potential inherited metabolic disorders. cblC deficiency is the most common type of methylmalonic aciduria in China. The late-onset patients present with varied non-specific symptoms and usually being misdiagnosed. The purpose of this study is to investigate the clinical features of patients with adolescence-onset cblC deficiency and explore the prevention and control strategies. Methods: Fifty-seven patients (34 males and 23 females) with adolescence-onset cblC deficiency were admitted in our clinic from 2002 to September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome and genotypes-phenotypes correlation were examined.Results: The onset ages ranged from 10 to 25 years old (median age was 12 years). 16 cases (28.0%) presented with symptoms after infection or sports training. 46 patients (80.7%) had neuropsychiatric diseases. 14 patients (24.6%) displayed cardiovascular diseases. Five cases (8.9%) showed pulmonary hypertension. Renal damage was observed in seven cases (12.3%). 23 mutations were identified from the MMACHC gene of 57 patients. 37 patients demonstrated c.482G>A (64.9%) and 16 cases had c.609G>A (26.3%). Among 13 patients that exhibited spastic paraplegia as a main manifestation, 10 patients had c.482G>A (76.9%). Five patients presented with psychotic disorders and spastic paraplegia with c.482G>A. All patients improved after metabolic treatment with cobalamin, L-carnitine, and betaine. 30 school-aged patients returned to school. Two patients were married and had healthy babies.Conclusion: Patients with adolescence-onset cblC deficiency presented with varied neuropsychiatric symptoms or multiple organ damage. Metabolic studies and individualized treatment are keys to improve the outcome of the patients.

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“…Disease Markers an intrathecal chemotherapy-treated boy who suffered from leukemia [37]. And any transient elevation of Hcy may be related to the seizure risk [38,39]. Although it is hard to determine whether the elevated Hcy is the cause or the result of a seizure, we offered neurosurgeons a new insight into the prophylactic and off-label utility of antiepileptic drugs.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Homocysteine Level on Neurological Outcome in Brain Arteriovenous Malformations

Lin

Zeng

et al. 2020

Disease Markers

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Objective. We aimed to investigate the serum homocysteine (Hcy) level in patients with brain arteriovenous malformation (bAVM) and their impact on neurological outcome during hospitalization. Method. We retrospectively reviewed patients diagnosed with bAVMs in Beijing Tiantan Hospital from January 2019 to August 2020. Patients were divided into two groups according to the mRS (modified Rankin Scale) score at discharge. Clinical and laboratory characteristics were compared. Logistic regression analyses were performed to identify the potential risk factors for short-term neurological outcome. Results. A total of 175 bAVM patients were enrolled in the study, including 139 patients with favorable outcome ( mRS ≤ 2 ) and 36 patients with unfavorable outcome ( mRS > 2 ). Hyperhomocysteinemia was identified in 32.6% of cases ( n = 57 ). Serum Hcy level was related to seizure manifestation ( P = 0.034 ) and short-term neurological outcome ( P = 0.027 ). Logistic regression analysis showed that serum glucose (OR 1.897, 95% CI 1.115-3.229; P = 0.018 ) and Hcy level (OR 0.838, 95% CI 0.720-0.976; P = 0.023 ) were significantly associated with short-term disability. Conclusion. Our results indicated that the lower serum Hcy level is strongly associated with in-hospital unfavorable outcome. Further prospective studies of Hcy natural history and managements in bAVMs are required, which would be valuable for evaluating the disease-modifying efficacy of oral nutritional supplements in bAVM patients.

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Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases

Cited by 22 publications

References 39 publications

Outcomes of patients with cobalamin C deficiency: A single center experience

Outcomes of patients with cobalamin C deficiency: A single center experience

Easily Misdiagnosed cblC Deficiency in Adolescents: the Clinical and Metabolic Studies

Prognostic Significance of Homocysteine Level on Neurological Outcome in Brain Arteriovenous Malformations

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