Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis.

Oberholzer, V. G.; Levin, B.; Burgess, E. Ann; Young, W. F.

doi:10.1136/adc.42.225.492

Cited by 312 publications

(136 citation statements)

References 10 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…An effect on the malate carrier at higher concentrations might be theoretically interesting; however, it is questionable whether this effect has any relevance for the pathophysiology of methylmalonic acidurias. Apart from this, MMA was shown to inhibit pyruvate carboxylase (34) and Na ϩ /K ϩ -ATPases (35).…”

Section: Discussionmentioning

confidence: 98%

Methylmalonic Acid, a Biochemical Hallmark of Methylmalonic Acidurias but No Inhibitor of Mitochondrial Respiratory Chain

Kölker¹,

Schwab²,

Hörster³

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Methylmalonic acidurias are biochemically characterized by an accumulation of methylmalonic acid and alternative metabolites. An impairment of energy metabolism plays a key role in the pathophysiology of this disease, resulting in neurodegeneration of the basal ganglia and renal failure. It has become the subject of intense debates whether methylmalonic acid is the major toxin, inhibiting respiratory chain complex II. To elucidate whether methylmalonic acid is a respiratory chain inhibitor, we used spectrophotometric analysis of complex II activity in submitochondrial particles from bovine heart, radiometric analysis of 14 C-labeled substrates (pyruvate, malate, succinate), and analysis of ATP production in muscle from mice. Methylmalonic acid revealed no direct effects on the respiratory chain function, i.e. on single electron transferring complexes I-IV, ATPase, and mitochondrial transporters. However, we identified a variety of variables that must be carefully controlled to avoid an artificial inhibition of complex II activity. In summary, the study verifies our hypothesis that methylmalonic acid is not the major toxic metabolite in methylmalonic acidurias. Inhibition of respiratory chain and tricarboxylic acid cycle is most likely induced by synergistically acting alternative metabolites, in particular 2-methylcitric acid, malonic acid, and propionyl-CoA.

show abstract

Section: Discussionmentioning

confidence: 98%

Methylmalonic Acid, a Biochemical Hallmark of Methylmalonic Acidurias but No Inhibitor of Mitochondrial Respiratory Chain

Kölker¹,

Schwab²,

Hörster³

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Progression to coma is not uncommon. If the patient does not succumb to the initial metabolic decompensation, failure to thrive, developmental retardation, renal failure and metabolic strokes follow [1,[3][4][5][6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Combined liver–kidney transplant for the management of methylmalonic aciduria: A case report and review of the literature

Guire

Lim-Melia

Diaz

et al. 2008

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Over 27 cases of liver transplant, kidney transplant and combined liver-kidney transplant have been reported for the treatment of methylmalonic aciduria. We describe a case of a 5-year-old boy who underwent combined liver-kidney transplant (CLKT) for phenotypic mut0 disease. His history was notable for more than 30 hospitalizations for severe acidosis, metabolic strokes, liver disease, pancreatic disease, chronic renal insufficiency with interstitial nephritis, and decreased quality of life. Post-CLKT, there was a marked reduction in serum (80%) and urine MMA levels (90%) as well as a cessation of metabolic decompensations. Neurologic deterioration continued post-CKLT manifested as a cerebellar stroke. The clinical details and therapeutic implications of solid organ transplant for methylmalonic aciduria are discussed.

show abstract

“…Propionate has some hypoglycemic effect under certain circumstances 22 . The mechanism of action of propionate at cellular level in isolated rat hepatocytes 23 is related to a decrease in gluconeogenesis 24 , inhibition of pyruvate carboxylase, which in turn is inhibited by metabolic products of propionate, the methylmalonyl-CoA and succinyl CoA 25 .…”

Section: Experimental Studiesmentioning

confidence: 99%

Fructo-oligosaccharide effects on blood glucose: an overview

2012

View full text Add to dashboard Cite

PURPOSE:To identify the current status of scientific knowledge in fructo-oligosaccharides (FOS), non-conventional sugars that play an important role in glycemia control. METHODS:We performed a search for scientific articles in MEDLINE and LILACS databases, from January 1962 to December 2011, using English/Portuguese key words: "blood glucose/glicemia", "prebiotics/prebióticos" and "dietary fiber/fibras na dieta". From an initial number of 434 references, some repeated, 43 references published from 1962 to 2011 were included in this study. The selected texts were distributed in three topics: (1) metabolism of FOS, (2) FOS and experimental studies involving glucose and (3) human studies involving glucose and FOS. RESULTS:Five studies have shown that the use of FOS reduces the fecal content and increases intestinal transit time. Experimental studies have shown that dietary supplementation with high doses (60 g/Kg) of propionate, a short-chain fatty acid decreased glycemia.The use of lower doses (3 g/kg) did not produce the same results. Study in subjects with diabetes type II showed that the addition of 8 grams of FOS in the diet for 14 days, caused a reduction in serum glucose. In another study with healthy subjects, there were no changes in glycemic control. CONCLUSIONS:This review demonstrates that consumption of FOS has a beneficial influence on glucose metabolism. The controversies appear to be due to inadequate methodological designs and/or the small number of individuals included in some studies.Key words: Review. Blood Glucose. Oligosaccharides. Prebiotics. Dietary Fiber. RESUMO OBJETIVO:Conhecer o estado atual do conhecimento científico em fructooligossacarídeos (FOS), açúcares não-convencionais que desempenham um papel importante no controle da glicemia. MÉTODOS: Realizamos uma busca de artigos científicos nas bases de dados MEDLINE e Literatura Latino-Americana e do Caribe emCiências da Saúde (LILACS), a partir de janeiro 1962 a dezembro de 2011, usando como descritores termos Português/Inglês: "glicemia/ blood glucose, "prebióticos/prebiotics" e "fibras na dieta/dietary fiber. A partir de um número inicial de 434 referências, algumas repetidas, 43 referências foram consideradas adequadas para a finalidade deste estudo e foram, portanto, selecionadas para análise. Os textos selecionados foram distribuídos em três tópicos: (1) metabolismo de FOS (2), FOS e estudos experimentais envolvendo glicose e (3) estudos em humanos envolvendo glicose e FOS. RESULTADOS: Cinco trabalhos mostraram que o uso de FOS diminui o conteúdo fecal e aumenta o tempo do transito intestinal.Estudos experimentais demonstraram que a suplementação dietética com altas doses (60 g/Kg) de propionato, um ácido graxo de cadeia curta, diminuiu a glicemia. A utilização de doses menores (3 g/Kg) não produziu os mesmos resultados. Em indivíduos diabéticos tipo II a adição de 8 g de FOS na dieta, durante 14 dias, induziu uma redução da glicemia. Em indivíduos sadios, não ocorreram alterações da glicemia. CONCLUSÕES:Essa revisão mostra...

show abstract

Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis.

Cited by 312 publications

References 10 publications

Methylmalonic Acid, a Biochemical Hallmark of Methylmalonic Acidurias but No Inhibitor of Mitochondrial Respiratory Chain

Methylmalonic Acid, a Biochemical Hallmark of Methylmalonic Acidurias but No Inhibitor of Mitochondrial Respiratory Chain

Combined liver–kidney transplant for the management of methylmalonic aciduria: A case report and review of the literature

Fructo-oligosaccharide effects on blood glucose: an overview

Contact Info

Product

Resources

About