GUANIDINO COMPOUNDS IN GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY,A NEW INBORN ERROR OF CREATINE SYNTHESIS

The first inborn error of creatine metabolism (guanidinoacetate methyl transferase [GAMT] deficiency) has recently been recognized in an infa nt with progressive extrapyramidal movement disorder. The diagnosis wa s established by creatine deficiency in the brain as detected by in vi vo magnetic resonance spectroscopy and by defective GAMT activity and two mutant GAMT,alleles in a liver biopsy. Here, we describe character istic guanidino-compound patterns in body fluids of this index patient with GAMT deficiency. Concentrations of guanidino compounds (creatine and guanidinoacetate) and creatinine were determined by cation-exchan ge chromatography and by color reaction with picric acid, respectively , in urine, plasma, and cerebrospinal fluid (CSF). Creatine concentrat ions were low in plasma, CSF, and urine while guanidinoacetate concent rations were markedly elevated. Daily urinary creatinine excretion was low, whereas creatinine concentrations in random urine samples were n ot always discriminative. Guanidino compound to creatinine ratios were not informative, as low creatinine concentrations resulted in high va lues for all determined compounds. During a 22-month period of oral tr eatment with creatine-monohydrate, plasma and urinary creatine concent rations increased to levels high above the normal range, and daily uri nary creatinine excretion-proportional to total body creatine-became n ormalized. Guanidinoacetate concentrations; remained elevated even dur ing additional substitution of ornithine, which inhibits guanidinoacet ate synthesis in vitro. The results indicate that GAMT deficiency can be recognized noninvasively by determination of guanidino compounds (c reatine and guanidinoacetate) in body fluids. A deficiency of creatine , but not an accumulation of guanidinoacetate, can be corrected by tre atment with oral creatine substitution. Copyright (C) 1997 by W.B. Sau nders Company.