The abnormal metabolites-adipic, suberic, and sebacic
acids-were detected in large amounts in the urine of a boy during a
Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic
acid, caproylglycine,
glutaric acid, and 3-OH-butyric
acid and moderately elevated amounts of
ethylmalonic acid,
methylsuccinic acid, 3-OH-isovaleric
acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack. 1-[14C]-
Palmitic acid was oxidized at a normal rate, whereas U-[14C]-
Palmitic acid was oxidized at a reduced rate in cultured skin fibroblasts from the patient, thus indicating a defect at the level of medium- and/or
short-chain fatty acid oxidation.
Riboflavin medication (100 mg three times a day) significantly reduced the excreted amounts of pathologic metabolites, suggesting a flavineadeninedinucleotide-related
acyl-CoA dehydrogenation defect as the cause of the disease.
Carnitine in plasma was low in the patient (6 mumole/liter, controls 26-74 mumole/liter), suggesting
carnitine deficiency as a secondary effect of the
acyl-CoA dehydrogenation deficiency. The present patient, who presented with a
Reye's syndrome-like attack, suffers from impaired dehydrogenation of
acyl-CoA resulting in accumulation of
acyl-CoA in the cells. Attacks with similar symptoms are seen in other
acyl-CoA dehydrogenation deficiencies, such as glutaric aciduria types I and II, other types of C6-C10-dicarboxylic acidurias and
isovaleric acidemia. Reduced flow through the
acyl-CoA dehydrogenation steps may therefore be an ethiologic factor in
Reye's syndrome. Several of the accumulated
acyl-CoA's are toxic and may be responsible for some of the symptoms. The low
carnitine level in plasma and the elevated esterified
carnitine excretion in the present patient indicate that
acyl-CoA accumulation may cause a functional
carnitine deficiency by sequestration of
carnitine as acyl-carnitines. As the inborn defect,
systemic carnitine deficiency may exhibit symptoms like those of
Reye's syndrome, it may be speculated whether functional
carnitine deficiency in patients with accumulated
acyl-CoA is another causal factor in the development of the symptoms during attacks.