Creatine deficiency in the brain : a new, treatable inborn error of metabolism

• Published in: Pediatric research Vol. 36; no. 3; pp. 409 - 413
• Main Authors: STÖCKLER, S, HOLZBACH, U, HANEFELD, F, MARQUARDT, I, HELMS, G, REQUART, M, HÄNICKE, W, FRAHM, J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.09.1994
• Subjects: Arginine - therapeutic use; Biological and medical sciences; Brain - metabolism; Clinical Medicine; Creatine - deficiency; Creatine - therapeutic use; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Infant; Klinisk medicin; Magnetic Resonance Spectroscopy - methods; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Metabolism, Inborn Errors - drug therapy; Neurology; Pediatrics; Pediatrik; Phosphocreatine - deficiency; Human; Nervous system diseases; Replacement therapy; Pathogenesis; Deficiency; Metabolic diseases; Infant; NMR spectrometry; Creatine; Cerebral disorder; Case study; Arginine; Central nervous system disease; Aminoacid disorder; Brain (vertebrata); Extrapyramidal syndrome
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1203/00006450-199409000-00023

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.