Propionic acidaemia

this being supported by observations on patients with propionic acidaemia (Childseta/., 1961 Ando eta/., 1972a). The potential importance of propionate synthesis by gut bacteria has also been discussed (Tanaka, 1975). 

The identity of propionic acidaemia with ketotic hyperglycinaemia was confirmed by Gompertz et al. (1970), who reported the second case of propionic acidaemia, a male child of first-cousin Pakistani parents, and correlated the clinical and biochemical observations of propionic acidaemia, hyperglycinaemia, accumulation of odd-carbon-number fatty acids (Ci5 0, Ci7 0, Ci7 1), and butanonuria, with an activity of propionyl-CoA carboxylase in liver mitochondria in vitro of only 10 per cent of that of control. The child died at 8 days of age. 

Propionyl-CoA carboxylase is expressed in both fibroblasts and cultured amniotic cells, and this has enabled prenatal diagnosis of the condition to be undertaken. Gompertz et al (1973, 1975) reported the detection of a foetus affected with propionic acidaemia in a mother in whom amniocentesis was performed at about 26 weeks gestation. Because of the time of amniocentesis, pregnancy proceeded and the affected infant was born at 38 weeks. Despite therapy with biotin and a low-protein (MSUD) diet the child died at 1 year of age. 

Hsia et al (1976) reported the prenatal detection of two foetuses at risk for propionic acidaemia, but who showed partially reduced activities of propionyl-CoA carboxylase in cultured amniotic cells, consistent with heterogeneity, confirmed at term, and this has also been the experience of the authors. 

The earlier reports on patients with chronic propionic acidaemia associated with ketotic hyperglycinaemia tended to concentrate on the occurrence, origin and possible significance of individual metabolites, thereby tending to impart 

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Van Hove JL, Chace DH, Kahler SG, Millington DS (1993) Acylcarnitines in amniotic fluid application to the prenatal diagnosis of propionic acidaemia. J Inherit Metab Dis 16 361-367... 

Propionic acidaemia (ketonic hyper- Propionic, 3-hydroxypropionic, 2-methyl-... 

Multiple carboxylase deficiency Non-ketotic hyperglycinaemia S-Oxoprolinuria Phenylketonuria Propionic acidaemia... 

Propionic acidaemia This is caused by deficiency of enzymes involved in the metabolism of propionyl coenzyme A... 

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. 

Rafique M. Propionic acidaemia demographic characteristics and complications. J Pediatr Endocrinol Metab. 2013 26(5-6) 497-501. 

Lee TM, et al. Unusual presentation of propionic acidaemia as isolated cardiomyopathy. J Inherit Metab Dis. 2009 32 Suppl LS97-101. 

Al-Hassnan ZN, et til. The relationship of plasma gluteunine to ammonium and of glycine to add-base beileuice in propionic acidaemia. J Inherit Metab Dis. 2003 26(1) 89-91. 

Schwahn BC, et aL Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia. Eur J Pediatr. 2010 169(1) 133. ... 

Abacan M, Boneh A. Use of caiglumic acid in the treatment of hyperammonaemia during metabolic decompensation of patients with propionic acidaemia. Mol Genet Metab. 2013 109(4) 397-401. 

Mayatepek E, Schulze A. Metabolic decompensation and lactic acidosis in propionic acidaemia complicated by thieunine deficiency. J Inherit Metab Dis. 1999 22(2) 189-90. 

An amino acid found in elevated amounts in blood and urine in the inborn errors of metabolism, non ketotic hyperglycinaemia, (which is possibly due to a deficiency in the enzyme glycine decarboxylase) and propionic acidaemia (ketotic hyperglycinaemia). It is also found in increased amounts in urine along with proline and hydroxyproline in another inborn error, familial iminoglycinuria. This is due to defective membrane transport of these amino acids. 

Figure 7 Fast atom bombardment mass spectra obtained in glycerol matrix for quantitation of free carnitine and carnitine esters in the urines of a patient with medium-chain acyl-CoA dehydrogenase deficiency (A) and a patient with propionic acidaemia (B). The identities and concentrations of the annotated ions are listed in Table 2. The composition of the ions has been confirmed by measurements...

Janovsky, U., Scholl-Btirgi, S., Karall, D. et al. (2005) Breath gas analysis in patients suffering from propionic acidaemia [Chapter 28]. In Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring (Eds A. Amann, D. Smith), World Scientific, Singapore. 

Chalmers, R.A., Bickle, S. and Watts, R.W.E. (1974a), A method for the determination of volatile organic acids in aqueous solutions and urine, and the results obtained in propionic acidaemia, )S-methylcrotonylglycinuria and methylmalonic aciduria. Clin. Chim. Acta, 52,31. 

Propionic acidaemia Propionic, 3-hydroxypropionic, Propionyl-CoA carboxylase methylcitric, 3-hydroxy-/i-valeric (ATP-hydrolysing) acids and propionylglycine. Glycine (EC 6.4.1.3) 11.1... 

Robert, M.F., Schultz, D.J., Wolf, B., Cochran, W.D. and Schwartz, A.L. (1979), Treatment of a neonate with propionic acidaemia and severe hyperammonaemia by peritoneal dialysis. Arch. Dis. Childh., 54,962. 

Sweetman, L., Weyler, W., Shafai, T., Young, P.E. and Nyhan, W.L. (1976), Prenatal diagnosis of propionic acidaemia by organic acid analysis. Clin. Res., 24, 295A (Abstract). 

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). 

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