Organic acid disorders

Schulze-Bergkamen A, Okun JG, Spiekerkotter U, et al (2005) Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids biochemical confirmation of fatty acid oxidation and organic acid disorders. Pediatr Res 58 873-880... 

Fig. 8.4 An abnormal urine organic acid profile indicat- acidemia (and organic acid disorder of leucine metabo-...

Unlike many routine clinical chemistry tests, clinical analyses of lEM almost always involve a multiple metabolite analysis. The results form the basis of a metabolic profile in which both individual concentrations of metabolites and their relationship to each other can be viewed either in tabular form or in a graphical display. Perhaps the most comprehensive and historically significant test in lEM studies is gas chromatography/mass spectrometry (GC/MS) of a derivatized extract of urine. Figure 2 is a chromatogram from an infant with propionic acidemia, an organic acid disorder of leucine metabolism. Hundreds of volatile compounds of carbohydrate, amino acid, fatty acid, and nucleic acid metabolism are separated in 40 min using capillary GC. Addition... 

Amniotic fluid has limited value in prenatal diagnosis for the aminoacid-opathies. Unlike the organic acid disorders, in most amino acid disorders the metabolites do not accumulate before birth. Abnormal amino acid patterns in amniotic fluid have only been found in two of the urea cycle disorders, namely argininosuccinate lyase deficiency (argininosuccinic acidemia) and argininosuccinate synthetase deficiency (citrullinemia). 

The range of clinical and biochemical findings in organic acid disorders is extensive (Table C.4). Provisionally, it appears helpful to consider two main types of clinical presentations Systemic intoxication or severe acute encephalopathy, which is the most common presentation (overview in [11]). The first episode usually occurs in (early) infancy, but it can also develop later in older children. Alternatively, older children can present with (sub-)acute neurological disease or variable fluctuating multisystemic manifestations. The former is the classical presentation of the cerebral organic acid disorders. 

In acute severe systemic intoxication abnormalities of routine clinical chemistry are usually present such as metabolic acidosis, increased anion gap, cytopenia, hypoglycemia, hyperammonemia (which can mask acidosis), lactic acidemia, elevations of triglycerides and free fatty acids, and ketosis. Testing for ketonuria is an especially simple and useful first line investigation. In most newborns as well as in older children with organic acid disorders, including some patients with fatty acid oxidation defects, there is pronounced ketonuria. Ketonuria is only rarely observed even in very sick newborns without metabolic disease. 

Screening for organic acid disorders (no urine available)... 

High clinical suspicion for organic acid disorders with possibly isolated elevations of pathological metabolites in CSF ( cerebral lactic addemiasj glutaryl-CoA dehydrogenase deficiency disorders of biotin metabolism)... 

Patients with organic acid disorders manifesting neurological disease... 

Note-. (1-9) Organic acid disorders, (10-14) fatty acid oxidation disorders, (15-20) amino acid disorders, (21-23) hemoglobinopathies, (24 and 25) endocrinopathy, (26) other inborn error of metabolism, (27) carbohydrate disorders, (28) miscellaneous genetic conditions, and (29) infectious diseases. MS/MS tandem mass spectrometry, HPLC high pressure hquid chromatography, lEF isoelectrofocusing, RIA radioimmuno assay, and ELISA enzyme-linked immunosorbent assay. 

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