Aciduria propionate disorders

Glycerol kinase deficiency HMG-CoA lyase deficiency Methylmalonic aciduria Mitochondrial disorders 2-oxoadipic aciduria Propionic aciduria Additional causes Bacterial production MCT containing formulas Riboflavin deficiency (acquired)... 

An important aspect of metabolite profiles is the study of known inborn errors where the qualitative and quantitative interrelationship of the affected metabolites can be studied. A recent example of this is the comparative study of three diseases, )8-methylcrotonylglycinuria, propionic acidemia and methylmalonic aciduria [362]. The advantage of considering a complete class of compounds in a single experiment is that biochemical markers for a disorder can be detected in the context of any variations in other components. This is particularly important in monitor-... 

Inborn errors of metabolism may be due to propionyl-CoA carboxylase deficiency, defects in biotin transport or metabolism, methylmalonyl-CoA mutase deficiency, or defects in adenosylcobalamin synthesis. The former two defects result in propionic acidemia, the latter two in methylmalonic acidemia. All cause metabolic acidosis and developmental retardation. Organic acidemias often exhibit hyperammonemia, mimicking ureagenesis disorders, because they inhibit the formation of N-acetylglutamate, an obligatory cofactor for carbamoyl phosphate synthase (Chapter 17). Some of these disorders can be partly corrected by administration of pharmacological doses of the vitamin involved (Chapter 38). Dietary protein restriction is therapeutically useful (since propionate is primarily derived from amino acids). Propionic and methylmalonyl acidemia (and aciduria) results from vitamin B12 deficiency (e.g., pernicious anemia Chapter 38). 

Methylc rotonylglycinur ia 3-Methylglutaconic aciduria, other types Biotinidase def 3-Oxothiolase def Methylmalonic acidemia Propionic acidemia L-2-Hydroxyglutaric aciduria Urea cycle disorders... 

In the metabolism of L-leucine, the isovaleryl-CoA produced by the oxidative decarboxylation step is further metabolized by a series of enzyme-catalysed steps to acetoacetate and acetyl-CoA and thence into the tricarboxylic acid cycle. Specific enzyme deficiencies at every stage of this metabolic pathway are known and are described in Section 10.3. In contrast, only one disorder of L-isoleucine metabolism subsequent to the oxidative decarboxylation step has been recognized (Section 10.4), and no disorders of the L-valine pathway from isobutyryl-CoA have been described. This may be due to their relative rarity but possibly also to greater difficulty in their detection. The metabolism of valine and leucine is, however, of particular interest in the organic acidurias, since both are major precursors of propionyl-CoA and methylmalonyl-CoA, defects in the metabolism of which lead to propionic acidaemia and methylmalonic aciduria (Chapter 11). 

This chapter is concerned with the known disorders in the metabolism of the branched-chain amino acids after the initial transamination step, that lead to abnormal organic aciduria. Disorders of propionate and methylmalonate metabolism are discussed separately in Chapter 11. 

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