Creatine metabolism during metabolic perturbations in patients with organic acidurias.

Creatine excretion was measured in two patients with methylmalonic aciduria and two patients with 3-hydroxy-3-methylglutaric aciduria. During periods of metabolic decompensation the creatine/creatinine ratio increased and fell during recovery. Prolonged periods of metabolic decompensation may result in the loss of a large proportion of the creatine pool. In one study, measurements of total daily urinary output of metabolites demonstrated that the absolute creatine excretion followed a similar qualitative pattern to the creatine/creatinine ratio. However, apparent fluctuations in methylmalonate excretion when expressed as methylmalonate/creatinine ratio were absent when absolute methylmalonate excretion was calculated. The increased creatine excretion during metabolic perturbations may result from loss from creatine containing tissues such as muscle and may represent an underlying defect in energy metabolism. Alternatively creatine transport may be disrupted by accompanying acidosis. The use of metabolite/creatinine ratios as a measure of metabolite excretion rates during metabolic decompensation whilst qualitatively sound may need a re-appraisal.