Different mutations in the <i>MMUT</i> gene are associated with the effect of vitamin B12 in a cohort of 266 Chinese patients with mut‐type methylmalonic acidemia: A retrospective study

Yu, Yue; Shuai, Ruixue; Liang, Lili; Qiu, Wenjuan; Shen, Linghua; Wu, Shengnan; Wei, Haiyan; Chen, Yongxing; Yang, Chenghui; Xu, Peng; Chen, Xigui; Zou, Hui; Feng, Jie; Niu, Tingting; Hu, Hejing; Ye, Jun; Zhang, Huiwen; Lu, Deyun; Gong, Zhuwen; Zhan, Xia; Ji, Wenjun; Gu, Xuefan; Han, Lianshu

doi:10.1002/mgg3.1822

Cited by 11 publications

(9 citation statements)

References 33 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, patients with MMUT gene mutations respond differently to vitamin B12 treatment, which may be related to the effect of vitamin B12 treatment with different gene mutation types and sites. Patients with reactive and partial response have a better prognosis, while those who do not respond to vitamin B12 develop the disease earlier, with the rst symptoms primarily accumulating in the central nervous system (43).…”

Section: Discussionmentioning

confidence: 99%

Clinical and electroencephalogram characteristics of methylmalonic acidemia with neurological injury

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective The study aims to investigate the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic academia (MMA) with nervous system damage as the primary manifestation.Methods From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation diagnosed as methylmalonic acidemia by hematuria metabolism or genetic test were collected and analyzed. Their clinical data, imaging data, and electroencephalogram data were analyzed.Result A total of 22 patients were enrolled, including 18 males and 4 females. The clinical symptoms included convulsions, developmental delay, feeding difficulties, poor feeding, disturbance of consciousness, abnormal movement (including involuntary movement, decreased muscle strength, and motor incoordination), and hypotonia. There were 8 cases (36%) of hydrocephalus, 2 cases (9%) of exencephaly effusion, 5 cases (22%) of corpus callosum dysplasia, 5 cases (22%) of myelination dysplasia, 1 case (4%) of abnormal frontal lobe signal, 1 case (4%) of decreased hippocampal volume, 6 cases (27%) of the abnormal lateral ventricular signal. Furthermore, 3 cases (13%) had abnormal signals in the basal ganglia. Also, there were 3 cases (13%) of cerebral atrophy/small parenchymal volume and 1 case (4%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data showed that there were 2 cases (9%) of hyper arrhythmia, 7 cases (31%) of voltage reduction, 13 cases (59%) of abnormal discharge, 15 cases (68%) of abnormal sleep physiological wave or abnormal sleep structure, 1 case (4%) of immature (delayed) EEG development, and 12 cases (54%) of slow background. There were 2 cases (9%) of spasms, 1 case (4%) of atonic seizures, and 1 case (4%) of myoclonic seizures. There were 20 patients (90%) with hyperhomocysteinemia. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral therapy. Acute treatment included anti-infective, blood transfusion, gamma globulin, fluid replenishment, correcting acidosis, and other treatments. Other treatments include low protein diets, special formula milk powder, and antiepileptic treatment.Conclusion Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals in head MRI. Hematuric metabolic screening and genetic testing help make the diagnosis clear. EEG can reflect the changes in brain function in the acute phase. With the remission of the disease, the electroencephalogram can return to normal. However, the children may still experience some deterioration in development.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and electroencephalogram characteristics of methylmalonic acidemia with neurological injury

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…For example, an improvement in clinical symptoms and a signi cant (> 50%) reduction in the blood C3/C2 ratio and urinary methylmalonic acid level after the vitamin B12 loading test are considered indicative of complete responsiveness. If the blood C3/C2 ratio and urinary methylmalonic acid levels decrease by < 50% but > 30%, it was deemed as partly vitamin B12 responsive [21] . Otherwise, the injection of vitamin B12 was considered non-responsive if a decreased value in the blood C3/C2 ratio and urinary methylmalonic acid were < 30%.…”

Section: Evaluation Of the Responsiveness To Vitamin B12mentioning

confidence: 99%

Clinical outcomes of patients with mut-type methylmalonic acidemia identified through expanded newborn screening in China

Ling,

Wu,

Shuai

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. Design & Methods In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. Results By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality. Conclusions This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.

show abstract

“…MMA can be classified into two main types: combined MMA and isolated MMA, depending on the presence or absence of homocysteinemia. The incidence of MMA ranges from 1/20000–1/25000 worldwide [ 2 ], but varies among regions in China, from nearly 1/5589 to 1/35734 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Clinical presentations of combined MMA can vary significantly, ranging from fetal onset in utero to atypical onset in adults. However, most patients exhibit symptoms before the age of one, including anemia, growth retardation, epilepsy and metabolic dysfunction [ 3 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study

Su,

Sheng,

et al. 2024

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations. Methods We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays. We then performed genetic analysis to confirm the diagnosis and identify the causal variants. Results We confirmed the common clinical manifestations of MMA reported previously. We also described four rare MMA cases with unusual symptoms or genetic variants, such as pulmonary hypertension or limb weakness in late-onset patients. We identified 15 MMACHC and 26 MMUT variants in 57 patients, including 6 novel MMUT variants. Two patients had only one MMAA variant each, and one patient had mild MMA due to mitochondrial DNA depletion syndrome caused by a SUCLA2 variant. Among 12 critically ill patients, isolated MMA was associated with higher C3, blood ammonia, and acidosis, while combined MMA was linked to hydrocephalus on skull MRI. MMACHC c.658-660delAAG and MMUT c.1280G > A variants were correlated with more severe phenotypes. Conclusions Our study demonstrates the clinical and genotypic heterogeneity of MMA patients and indicates that metabolic screening and genetic analysis are useful tools to identify rare cases.

show abstract

Different mutations in the MMUT gene are associated with the effect of vitamin B12 in a cohort of 266 Chinese patients with mut‐type methylmalonic acidemia: A retrospective study

Cited by 11 publications

References 33 publications

Clinical and electroencephalogram characteristics of methylmalonic acidemia with neurological injury

Clinical and electroencephalogram characteristics of methylmalonic acidemia with neurological injury

Clinical outcomes of patients with mut-type methylmalonic acidemia identified through expanded newborn screening in China

Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study

Contact Info

Product

Resources

About