Dicarboxylic aciduria (DCA-uria) is a relatively common finding in the screening of organic acidemias by gas chromatography/mass spectrometry (GC/MS). A considerable number of patients with DCA-uria are involved in disturbances of mitochondrial and peroxisomal
fatty acid beta-oxidation. The differential diagnosis of DCA-uria was investigated using a combination of organic
acid analysis by GC/MS,
carnitine determination, acylcarnitines by fast atom bombardment/mass spectrometry (FAB/MS) and acylglycines by stable-
isotope dilution analysis. The relative distribution of urinary metabolites was examined in 46 patients with DCA-uria of different origins, including physiological
ketosis of childhood, disorders of
propionic acid metabolism,
glutaric aciduria type II,
Zellweger syndrome and patients who were clinically diagnosed as having
Reye syndrome.
Zellweger syndrome seemed to be distinguishable from other disorders by the high
sebacic acid/
adipic acid ratio of DCA-uria and increased excretion of
4-hydroxyphenyllactic acid and
2-hydroxysebacic acid. The mild form of
glutaric aciduria type II was often missed by current organic
acid analysis alone, but was readily diagnosed by
acylcarnitine and acylglycine determination. The ratio of free/total
carnitine was low in most of the DCA-uria patients except for two of five cases of
Zellweger syndrome and one of three cases of
Reye syndrome. The
acylcarnitine analysis by FAB/MS showed adipyl-, suberyl-, sebacyl- or dodecanedioylcarnitine as major peaks in most of these patients, although these were not specific. Disease-specific peaks were detectable only in congenital organic acidemias such as
glutaric aciduria type II,
methylmalonic acidemia and
propionic acidemia.