Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall

Guanidinoacetate methyltransferase (GAMT) deficiency (creatine deficiency syndrome) is a recently discovered inborn error of creatine biosynthesis. Affected patients have elevated concentrations of guanidinoacetate, the metabolic precursor of creatine, in urine, plasma and cerebrospinal fluid. In addition, urinary creatinine excretion and plasma creatinine concentration are decreased. For biochemical evaluation of patients suspected to suffer from GAMT deficiency, correct quantification of creatinine in plasma is important. Here we report our experience with different quantification techniques. We found that creatinine in plasma from two GAMT‐deficient patients appeared normal when measured by the Jaffé method but was decreased when measured enzymatically or by HPLC. The apparently normal levels of creatinine as measured by the Jaffé method were not caused by guanidinoacetate. In urine, the Jaffé method and the enzymatic method gave similar results, indicating that in urine no false elevations of creatinine can be expected. As the Jaffé method is still widely used for routine plasma creatinine measurements, it is important to realize it cannot be used to exclude GAMT deficiency.