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Methylmalonic Acid (methylmalonic + acid)
Selected AbstractsAtypical methylmalonic aciduria: frequency of mutations in the methylmalonyl CoA epimerase gene (MCEE),,HUMAN MUTATION, Issue 10 2007Abigail B. Gradinger Abstract Methylmalonic aciduria is known to result from defects in the enzyme methylmalonyl CoA mutase (MCM) (mut complementation group) and from defects in the synthesis of the MCM cofactor adenosylcobalamin (cblA, cblB, cblC, cblD, and cblF groups). Two patients who excrete methylmalonic acid have recently been shown to have a homozygous nonsense mutation in the gene coding for methylmalonyl CoA epimerase (MCEE). To further understand the cause of methylmalonic acid excretion, the MCEE gene was sequenced in 229 patients with elevations of methylmalonic acid excretion for which no cause was known. Mutations in MCEE were detected in five patients: two patients homozygous for c.139C>T, p.R47X, one patient homozygous for c.178A>C, p.K60Q, and two patients heterozygous for c.427C>T, p.R143C. Fusion of fibroblast lines from two patients homozygous for c.139C>T, p.R47X did not result in correction of [14C]propionate incorporation toward control values while the defect in these fibroblasts was complemented by mut, cblA, and cblB fibroblasts. Infection with wild-type MCEE cDNA resulted in correction of the biochemical phenotype in cells from both patients. © 2007 Wiley-Liss, Inc. [source] Metabolic Markers of Cobalamin Deficiency and Cognitive Function in Normal Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2004Angeles A. Garcia MD, FRCPC Objectives: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. Design: Cross-sectional study. Setting: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. Participants: Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older. Measurements: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). Results: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (,=,0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores. Conclusion: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine. [source] A population-based intervention study on elevated serum levels of methylmalonic acid and total homocysteine in elderly people: results after 36 months of follow-upJOURNAL OF INTERNAL MEDICINE, Issue 5 2004K. Björkegren Abstract. Objectives., To study the effects of vitamin B12 and folic acid treatment on haematological measures, reported symptoms and clinical findings over a 3-year period. Design., A longitudinal two-cohort study. Setting., A mid-Swedish community. Subjects., A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin <300 pmol L,1 and serum methylmalonic acid (MMA) ,0.37 ,mol L,1 or serum total homocysteine (tHcy) ,15 ,mol L,1 and who had no vitamin B12 or folic acid substitution were selected for treatment. Main outcome measures., Serum cobalamin, folate, MMA and tHcy. Presence of gastrointestinal, neurological, psychiatric and some other symptoms, obtained by questionnaire, and Mini Mental State Examination (MMSE) score, vibration sense measurement and findings at a physical examination. Results., After combined vitamin B12,folic acid treatment, all persons normalized their serum tHcy and MMA levels and the effect remained after 3 years. The study design allowed separation of pure vitamin B12 deficiencies from folate and combined deficiencies. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. No improvement was seen for other symptoms, reflex activity or MMSE score. Conclusions., Vitamin treatment of elderly people in the early phase of the condition may reverse damage that otherwise would become irreversible. If initiated, the treatment should be combined with vitamin B12 and folic acid. [source] Efficacy of Living Donor Liver Transplantation for Patients With Methylmalonic AcidemiaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007D. Morioka Application of liver transplantation to methylmalonic acidemia (MMAemia) is controversial because MMAemia is caused by a systemic defect of methylmalonyl-CoA mutase. The clinical courses of seven pediatric patients with MMAemia undergoing living donor liver transplantation (LDLT) were reviewed. Serum and urinary methylmalonic acid (MMA) levels were found to be significantly decreased after LDLT, whereas serum and urinary MMA levels did not return to normal in any patient. One patient died of sepsis 44 days after LDLT. The other six patients are currently doing well. All patients had preoperative history of acute metabolic decompensation and/or metabolic stroke. However, no episode of acute metabolic decompensation or metabolic stroke was observed postoperatively in any surviving patients. In the preoperative period, all patients showed lethargy and cognitive deficit, both of which were eradicated after LDLT in all surviving patients. Preoperatively, all patients were subjected to dietary protein intake restriction and tube feeding, and were administered several metabolism-correcting medications. The metabolism-correcting medications being administered remained mostly unchanged after LDLT, whereas protein restriction was liberalized and tube feeding became unnecessary in all surviving patients. In addition, physical and neurodevelopmental growth delay remained in all surviving patients during the observation period, which ranged from 4 to 21 months with a median of 10.5 months. [source] Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson diseaseANNALS OF NEUROLOGY, Issue 1 2010Cory Toth MD Objective Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels. Methods In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels. Results Fifty-eight randomly selected IPD patients were compared to 58 age- and sex-matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels. Interpretation IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. ANN NEUROL 2010;67:28,36 [source] Fingerprints of Damped Quantum Rotation Observed in Solid-State Proton NMR SpectraCHEMPHYSCHEM, Issue 4 2006Peter Gutsche Dr. Abstract 1H NMR spectra of the methyl group in an oriented crystal sample of methylmalonic acid with all three non-methyl protons replaced by deuterons are interpreted in terms of the damped quantum rotation (DQR) theory of NMR line shapes. The DQR approach offers a perfect theoretical reproduction of the observed spectra while the conventional Alexander-Binsch line-shape model shows evident defects in the present case. The temperature trends of the quantities characterizing the coherent and incoherent dynamics of the methyl group in the DQR approach (the effective tunnelling frequency and two coherence-damping rates) derived from the spectra are fairly reproduced using a model reported previously. The present findings provide further evidence of limitations to the validity of the common belief that molecular rate processes in condensed phases are necessarily classical. [source] | ||||||||||