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Search results for: MMACHC

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#38763872   2024/05/15 To Up

[Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia].

To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Among the 55 patients, 31 were males and 24 were females. The median age of onset was 12 years old (range 10-18 yearsold). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.
X Ma, Z H Chen, H T Zhang, R X He, Q Wang, Y Ding, J Q Song, Y Jin, M Q Li, H Dong, Y Zhang, M Lu, X P Lu, H Q Cao, Y Q Wang, Y X Chen, H Zheng, Y L Yang

2560 related Products with: [Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia].

500 MG500 mg10 mg 25 ml 50 ug 1 G

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#38750596   2024/05/15 To Up

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

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.
Ling Su, Huiying Sheng, Xiuzhen Li, Yanna Cai, Huifen Mei, Jing Cheng, Duan Li, Zhikun Lu, Yunting Lin, Xiaodan Chen, Minzhi Peng, Yonglan Huang, Wen Zhang, Li Liu

1209 related Products with: Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study.



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#38745823   2024/05/07 To Up

Severe heart failure in a unique case of cobalamin-C-deficiency resolved with LVAD implantation and subsequent heart transplantation.

Introduction Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. It usually leads to a multisystemic disease; 50% of all patients with cblC have various structural heart defects. Severe congestive heart failure (HF) may also occur and its prognosis is poorly documented. Case report We present the case of a young man who had been diagnosed with cblC due to C331T mutation in the MMACHC gene at the age of 3 days and had been treated with substitution therapy (OH-Cbl, mecobalamine, carnitine, betaine, and calcium folinate) since then. He had mildly impaired cognitive function; an ectopic hypophysis/pituitary insufficiency, with adequate hormone replacement therapy; obstructive sleep apnea syndrome, treated with CPAP, bronchial asthma, and obesity (BMI of 30). The liver and kidney functions were normal. He developed severe dilated cardiomyopathy and HF at the age of 12y. With medical treatment, his condition improved and he was stable (NYHA class II) for several years. Six years later, his status deteriorated rapidly, as he developed advanced HF, INTERMACS 3. The cardiac ultrasound revealed dilated ventricles with severely depressed ejection fraction (EF), increased filling pressures, and pulmonary hypertension (sPAP 60 mmHg). Cardiac MRI showed extremely dilated chambers (LVedv 609 mL, RVedv 398 mL) with pronounced non-compaction, and a left ventricle EF of 13%. A primary prophylactic ICD and a left ventricular assist device (LVAD/HM3) were implanted, and the patient was subsequently listed for heart transplantation (HTx). After 25 months on the waiting list, he underwent an uncomplicated HTx. However postoperatively, he got two episodes of cardiac tamponade, as well as mediastinitis, treated with antibiotics and vaccum assisted closure. He developed severe kidney failure, which fully recovered after two months, and was treated successfully for an early moderate allograft rejection (ISHT 2). At the latest outward visit, twelve months after HTx, the patient was doing excellent. Summary To the best of our knowledge, this is the first ever reported case of a patient with CblC undergoing an LVAD implantation and subsequently a HTx. Although both interventions were complicated with bleeding events, this seems to be a treatment option for advanced HF in patients with CblC.
Clara Hjalmarsson, Charlotte Backelin, Anders Thoren, Niklas Bergh, Jennifer L Sloan, Irini Manoli, Charles P Venditti, Göran Dellgren

2529 related Products with: Severe heart failure in a unique case of cobalamin-C-deficiency resolved with LVAD implantation and subsequent heart transplantation.

100 UG

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#38651393   2024/03/29 To Up

Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry.

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were (1:42), (1:51), (1:52), (1:55) and (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.
Chengfang Tang, Lixin Li, Ting Chen, Yulin Li, Bo Zhu, Yinhong Zhang, Yifan Yin, Xiulian Liu, Cidan Huang, Jingkun Miao, Baosheng Zhu, Xiaohua Wang, Hui Zou, Lianshu Han, Jizhen Feng, Yonglan Huang

2341 related Products with: Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry.

1 G1 LITRE 1 kit(s) 192 Tests n25 assays192 Tests n 100ul8 Sample Kit

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#38617190   // To Up

Overexpression of Prevents Craniofacial Phenotypes Caused by Knockdown of .

ZNF143 is a sequence-specific DNA binding protein that regulates the expression of protein-coding genes and small RNA molecules. In humans, ZNF143 interacts with HCFC1, a transcriptional cofactor, to regulate the expression of downstream target genes, including , which encodes an enzyme involved in cobalamin () metabolism. Mutations in or cause an inborn error of cobalamin metabolism characterized by abnormal metabolism, intellectual disability, seizures, and mild to moderate craniofacial abnormalities. However, the mechanisms by which mutations cause individual phenotypes are not completely understood. Defects in metabolism and craniofacial development are hypothesized to occur because of decreased expression of . But recent results have called into question this mechanism as the cause for craniofacial development. Therefore, in the present study, we implemented a loss of function analysis to begin to uncover the function of ZNF143 in craniofacial development using the developing zebrafish. The knockdown of , one zebrafish ortholog of , caused craniofacial phenotypes of varied severity, which included a shortened and cleaved Meckel's cartilage, partial loss of ceratobranchial arches, and a distorted ceratohyal. These phenotypes did not result from a defect in the number of total chondrocytes but were associated with a mild to moderate decrease in expression. Interestingly, expression of human MMACHC via endogenous transgene prevented the onset of craniofacial phenotypes associated with knockdown. Collectively, our data establishes that knockdown of causes craniofacial phenotypes that can be alleviated by increased expression of .
Isaiah Perez, Nayeli G Reyes-Nava, Briana E Pinales, Anita M Quintana

1174 related Products with: Overexpression of Prevents Craniofacial Phenotypes Caused by Knockdown of .

5 G96T48 assays

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#38562051   // To Up

Clinical application value of pre-pregnancy carrier screening in Chinese Han childbearing population.

To explore the clinical application value of pre-conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age.
Li Tan, Yuefan Qi, Peijuan Zhao, LanLan Cheng, Guo Yu, Dongmei Zhao, Yu Xia Song, Yun Gai Xiang

2185 related Products with: Clinical application value of pre-pregnancy carrier screening in Chinese Han childbearing population.



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#38387306   2024/02/10 To Up

The MMACHC variant c.158T>C: Mild clinical and biochemical phenotypes and marked hydroxocobalamin response in cblC patients.

Mutations in MMACHC cause cobalamin C disease (cblC, OMIM 277400), the commonest inborn error of vitamin B metabolism. In cblC, deficient activation of cobalamin results in methylcobalamin and adenosylcobalamin deficiency, elevating methylmalonic acid (MMA) and total plasma homocysteine (tHcy). We retrospectively reviewed the medical files of seven cblC patients: three compound heterozygotes for the MMACHC (NM_015506.3) missense variant c.158T>C p.(Leu53Pro) in trans with the common pathogenic mutation c.271dupA (p.(Arg91Lysfs*14), "compounds"), and four c.271dupA homozygotes ("homozygotes"). Compounds receiving hydroxocobalamin intramuscular injection monotherapy had age-appropriate psychomotor performance and normal ophthalmological examinations. In contrast, c.271dupA homozygotes showed marked psychomotor retardation, retinopathy and feeding problems despite penta-therapy (hydroxocobalamin, betaine, folinic acid, l-carnitine and acetylsalicylic acid). Pretreatment levels of plasma and urine MMA and tHcy were higher in c.271dupA homozygotes than in compounds. Under treatment, levels of the compounds approached or entered the reference range but not those of c.271dupA homozygotes (tHcy: compounds 9.8-32.9 μM, homozygotes 41.6-106.8 (normal (N) < 14); plasma MMA: compounds 0.14-0.81 μM, homozygotes, 10.4-61 (N < 0.4); urine MMA: compounds 1.75-48 mmol/mol creatinine, homozygotes 143-493 (N < 10)). Patient skin fibroblasts all had low cobalamin uptake, but this was milder in compound cells. Also, the distribution pattern of cobalamin species was qualitatively different between cells from compounds and from homozygotes. Compared to the classic cblC phenotype presented by c.271dupA homozygous patients, c.[158T>C];[271dupA] compounds had mild clinical and biochemical phenotypes and responded strikingly to hydroxocobalamin monotherapy.
Tanguy Demaret, Karine Bédard, Jean-François Soucy, David Watkins, Pierre Allard, Alina Levtova, Alan O'Brien, Catherine Brunel-Guitton, David S Rosenblatt, Grant A Mitchell

2963 related Products with: The MMACHC variant c.158T>C: Mild clinical and biochemical phenotypes and marked hydroxocobalamin response in cblC patients.

1000 tests1000 TESTS/0.65ml100ug

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#38355526   2024/02/14 To Up

Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.

This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation.
Yujun Yuan, Ying Ma, Qiong Wu, Liang Huo, Chun-Feng Liu, Xueyan Liu

1868 related Products with: Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.

100ug25 mg 5 G 5 G1 g0.1 mg96 wells (1 kit)100ul50 ug 200ul10 mg100 mg

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#38345966   // To Up

Clinical and Molecular Genetic Analysis with Methylmalonic Acidemia Combined with Homocystinuria.

Based on research, c.609G>A (p.W203X) is a universal mutation site for MMACHC in methylmalonic acidemia (MMA) combined with homocystinuria, cblC type (cblC disease), and c.467G>A (p.G156D) mutation in families with such disease have not yet been reported. To conduct clinical and molecular genetic analysis of a family with cblC disease.
Xinhui Gan, Yanhua Guo, Jie Shen, Yan Zhao, Fangfang Zhang, Chunmei Yu

1676 related Products with: Clinical and Molecular Genetic Analysis with Methylmalonic Acidemia Combined with Homocystinuria.

100ug1 module10 mg

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#38261977   // To Up

METHYLATION-ASSOCIATED PATHWAYS IN MACULAR TELANGIECTASIA TYPE 2 AND OPHTHALMOLOGIC FINDINGS IN PATIENTS WITH GENETIC METHYLATION DISORDERS.

Serine (Ser) and glycine (Gly) levels were reported to differ between patients with macular telangiectasia type 2 (MacTel) compared with healthy controls. Because they are closely related to methylation metabolism, this report investigates methylation-associated metabolite levels in patients with MacTel and retinal changes in monogenetic methylation disorders.
Laurenz Pauleikhoff, Victoria Wingert, Sarah C Grünert, Clemens Lange, Luciana Hannibal, Felicitas Bucher

2106 related Products with: METHYLATION-ASSOCIATED PATHWAYS IN MACULAR TELANGIECTASIA TYPE 2 AND OPHTHALMOLOGIC FINDINGS IN PATIENTS WITH GENETIC METHYLATION DISORDERS.

300 units100 ug96T5mg2250ul10mg25mg96T2000 pcs

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