Congenital disorders of metabolism show a wide spectrum of symptoms as a consequence of impairment of a certain metabolic pathway by mutated
enzymes resulting in abnormal accumulation of
enzyme substrates, deficiency of expected products, and abnormal burden to collateral metabolic pathways, etc. However, in some occasions, depending on which pathway up to what degree of disturbance, it can be asymptomatic until a certain kind of burden is placed on to the patient.
Enzyme deficiency involved in
pyrimidine degradation, such as
Dihydropyrimidine dehydrogenase (DPD) and
Dihydropyrimidinase (DHP), has been reported with convulsion or
autism as symptoms, but many asymptomatic cases are also reported. However, when the patients are treated with
5-fluorouracil, a
pyrimidine analogue anticancer
drug, lethal side-effects can be seen even in asymptomatic patients. Some oral cephem
antibiotics have
pivalic acid side chain to increase absorption rate at intestine. These
antibiotics degrade into active
antibiotics and
pivalic acid at the intestinal wall. This
pivalic acid is
carnitine-conjugated and excreted into urine.
Carnitine acts as a carrier of long chain
fatty acid to mitochondria and to beta-oxidation, thus an important molecule for energy production by beta-oxidation and maintenance of mitochondrial function. Because of this, long term administration of such
antibiotics could induce depletion of
carnitine from the body and lead to low ketotic
hypoglycemia, convulsion and consciousness disturbance. This paper reports some possible serious side effects closely linked to
drug metabolism.