Creatine deficiency in the brain: a new, treatable inborn error of metabolism.
In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatinine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of brain guanidinoacetate as the immediate precursor of creatine but did not elevate cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate led to a significant increase of brain creatine, a decrease of brain guanidinoacetate, and a normalization of creatinine in serum and urine. Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable creatine-phosphate before oral substitution of creatine and a significant increase afterward. Partial restoration of cerebral creatine concentrations was accompanied by improvement of the patient's neurologic symptoms. This is the first report of a patient with complete creatine deficiency in the brain. Magnetic resonance spectroscopy during arginine and creatine treatment point to an inborn error of creatine biosynthesis at the level of guanidinoacetete-methyltransferase.
Stöckler
S
S
Kinderklinik, Universität Göttingen, Germany.
Holzbach
U
U
Hanefeld
F
F
Marquardt
I
I
Helms
G
G
Requart
M
M
Hänicke
W
W
Frahm
J
J
D001120:Arginine / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D003401:Creatine / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy; D010725:Phosphocreatine / Q000172:deficiency*
D010725:Phosphocreatine; D001120:Arginine; D003401:Creatine