Disorders of organic acid metabolism

This in fact is what happened. Tandem MS has clearly been shown to be the only technology to screen for disorders of fatty acid oxidation and could also detect many disorders of organic acid metabolism. Tandem MS has the ability to detect both compound classes (amino acids and acylcarnitines) and after demonstrating that both classes could be prepared in the same manner, the MS/MS analysis of blood spots for newborn screening applications was born. 

Table 3.1.1 shows a summary of known disorders of organic acid metabolism... 

Table 3.1.1 Disorders of organic acid metabolism (in alphabetical order). This table does not include disorders with primary accumulation of amino acids, disorders of mitochondrial fatty acid oxidation, or primary lactic acidemias. Co A Coenzyme A, FAD flavin adenine dinucleotide...

Chalmers RA, Roe CR, Stacey , Hoppel CL (1988) Urinary excretion of L-carnitine and acylcarnitines by patients with disorders of organic acid metabolism evidence for secondary insufficiency of L-carnitine. Pediatr Res 18 1325-1328... 

Table 55-3 shows a summary of known disorders of organic acid metabolism, including information about their incidence, major clinical features and biochemical patterns, availability of prenatal diagnosis and newborn screening, and association with sudden unexpected death. The incidence of individual inborn errors of organic add metabolism varies from 1 10,000 to >1 1,000,000 live births. All possible disease entities included, the incidence of conditions in which informative organic acid profiles could be detected in urine is likely to approach 1 1000 live births. 

TAB1 E and Laboratory Characteristics of Disorders of Organic Acid Metabolism —Continue ... 

Chronic, recurrent) pancreatitis Hepatosplenomegaly Reye or "Reye-like syndromes Recurrent severe infections (Non-immune hemolytic) anemia Myeloproliferative syndrome (Cave Routine chemical abnormalities such as hypoglycemia, metabolic acidosis, lactic acidosis, hyperammonemia or ketonuria, the usual concomitants of disorders of organic acid metabolism, can be conspicuously absent in the last two categories)... 

Hoffmann GF, Gibson KM (1996) Disorders of organic acid metabolism. In Moser HW (ed) Handbook of Clinical Neurology Neurodystrophies and Neurolipidoses, Vol. 66, Elsevier Science Publishers, Amsterdam, pp 639-660... 

Tanaka, K. (1975), Disorders of organic acid metabolism. In The Biology of Brain... 

The most satisfactory derivative for gas chromatographing acylglycines, particularly those of dicarboxylic acids, is presently the methyl ester and these have been used in the analysis of several acylglycines occurring in disorders of organic acid metabolism [e.g. isovalerylglycine (Tanaka and Isselbacher,... 

Tanaka, K. (1975), Disorders of organic acid metabolism. In Biology of Brain Dysfunction (ed. G.E. Gaull), Vol. 3, Plenum Publishing Co., New York, pp. 145-214 (Chapter 3). 

Dixon, M., Macdonald, A. and White, F. (2001). Disorders of amino acid metabolism, organic acidaemias and urea cycle defects. In (eds V. Shaw and M. Lawson), Clinical Paediatric Dietetics, 2nd edn. Blackwell Science, Oxford UK, pp. 233-294. 

Interpretation of complex metabolic profiles and communication of lab results to clinicians has been one of the greatest challenges in dried blood spot analysis by MS/MS for acylcamitines and amino acids. Following its introduction, MS/MS defined numerous diseases of fatty acid and organic acid metabolism that were uncommonly encountered in a typical practice and not well understood by most pediatricians. Furthermore, even in disorders such as PKU that were well known, the improvements made by MS/MS screening for PKU compared with older technology such as BIA or fluorometry were not well... 

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). 

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