Methylmalonic Acidemia with Novel<i> MUT</i> Gene Mutations

Panigrahi, Inusha; Bhunwal, Savita; Varma, Harish T.; Singh, Simranjeet

doi:10.1155/2017/8984951

Cited by 5 publications

(4 citation statements)

References 5 publications

(5 reference statements)

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“…MUT gene mutation is the most common genotype of isolated MMA. In our case, the two isolated MMA were both MUT gene mutations, and there have been many reports about these two genetic variants [35][36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 73%

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

Yuan,

Ma,

et al. 2024

BMC Pediatr

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Objective This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (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 with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed. Results A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder. Conclusion Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.

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Section: Discussionmentioning

confidence: 73%

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

Yuan,

Ma,

et al. 2024

BMC Pediatr

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“…The disease can be defined by MS/MS and GC/MS. Cases of MMA that are due to mutations in the MMUT gene usually lead to a severe phenotype and a very poor prognosis [ 16 , 17 ]. However, the known mutations of MMUT can only explain part of the affected individuals.…”

Section: Discussionmentioning

confidence: 99%

Impaired Function of a Rare Mutation in the MMUT Gene Causes Methylmalonic Acidemia in a Chinese Patient

Dai

Yang

et al. 2022

Genetics Research

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Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder mainly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene (MMUT) and leads to the reduced activity of MCM. In this study, a 3-year-old girl was diagnosed with carnitine deficiency secondary to methylmalonic acidemia by tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GS/MS). Whole-exome sequencing (WES) was performed on the patient and identified two compound heterozygous mutations in MMUT: c.554C>T (p. S185F) and c.729–730insTT (p. D244Lfs ∗ 39). Bioinformatics analysis predicted that the rare missense mutation of c.554C>T would be damaging. Moreover, this rare mutation resulted in the reduced levels of MMUT mRNA and MMUT protein. Collectively, our findings provide a greater understanding of the effects of MMUT variants and will facilitate the diagnosis and treatment of patients with MMA.

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“…Liver transplantation has been proposed as a therapeutic modality. However, some discrepancies on the feasibility of liver transplantation exist in the literature [2,4].…”

Section: Discussionmentioning

confidence: 99%

“…Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder [1] that affects 1:48,000 to 1:61, 000 newborns in western population [2]. The disease usually presents with lethargy and signs of metabolic crisis including acidosis, hyperketonemia, hypo-or hyperglycaemia and hyperammonemia which may lead to multiorgan failure, coma and even death in the first year of life in affected individuals [3,4].…”

Section: Introductionmentioning

confidence: 99%

Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene

et al. 2020

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Background: Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. Case presentation: The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. Conclusions: Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

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Methylmalonic Acidemia with Novel MUT Gene Mutations

Cited by 5 publications

References 5 publications

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

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

Impaired Function of a Rare Mutation in the MMUT Gene Causes Methylmalonic Acidemia in a Chinese Patient

Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene

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