Methylmalonic acid inheritance

Lenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonic acid metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, NY, pp 2165-2193... 

Animal and human studies have shown that an elevated concentration of ammonia (hyperammonemia) exerts toxic effects on the central nervous system. There are several causes, both inherited and acquired, of hyperammonemia. The inherited deficiencies of urea cycle enzymes are the major cause of hyperammonemia in infants. The two major inherited disorders are those involving the metabolism of the dibasic amino acids lysine and ornithine and those involving the metabolism of organic acids, such as propionic acid, methylmalonic acid, isovaleric acid, and others (see Chapter 55). 

OMIM, Online Mendelian Inheritance in Man (www.ncbi.nlm.nih.gov/entrez/query.fcgiidb—OMIM) NBS, newborn screening MMA, methylmalonic acid GLY, glycine tHey, total homocysteine. 

The term phenocopy refers to an environmentally induced variation that closely resembles a genetically determined variation. For example, dietary vitamin B deficiency is a phenocopy of the inherited disorder, methylmalonic acidemia and homocystinuria due to cobalamin C disease. Both dietary vitamin B,2 deficiency and cobalamin C disease have the biochemical findings of elevated plasma methylmalonic acid and homocysteine levels. Awareness of phenocopies is important as they provide an alternative explanation for clinical findings. For example, in the case of elevated... 

Figure 1 The electron ionization total ion current chromatogram for the trimethylsilyl derivatives of the organic acids extracted from the urine of a patient with an inherited error of methylmalonyl-CoA mutase. The major acidic component is methylmalonic acid. The annotated peaks are identified in Table 1.

Gibson KM, Lee CF, Bennett MJ, Holmes B, Nyhan WL (1993) Combined malonic, methylmalonic and ethylmalonic acid semialdehyde dehydrogenase deficiencies an inborn error of beta-alanine, L-valine and L-alloisoleucine metabolism J Inherit Metab Dis 16 563-567... 

Chiandetti L, ZaccheHo F. Acute metabolic decompensation in methylmalonic acidosis time sequence in the urinary excretion pattern of precursor organic acids and their major metabolites. Perspect Inherit Metab Dis 1987 7 57-70. 

Yannicelli S. Nutrition therapy of organic acidaemias with amino acid-based formulas emphasis on methylmalonic and propionic acidaemia. J Inherit Metab Dis. 2006 29(2-3) 281-7. 

Propionic acidemia (PROP) and methylmalonic acidemia (MMA) are inherited disorders of the metabolism of the propiogenic amino acids valine, isoleucine, threonine, and methionine and odd-chain fatty acids (Figs. 20.1 and 20.2,... 

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