Bianchi M C, Tosetti M, Battini R, Leuzzi V, Alessandri' M G, Carducci C, Antonozzi I, Cioni G
Department of Neuroradiology, Santa Chiara Hospital, Pisa, Italy.
AJNR Am J Neuroradiol. 2007 Mar;28(3):548-54.
Brain creatine (Cr) deficiencies (BCr-d) are rare disorders of creatine biosynthesis and transport. We performed consecutive measures of total Cr (tCr) and of its phosphorylated fraction, phosphocreatine (PCr), in the brains of children affected by Cr synthesis defects during a long period of therapy. The aim was to identify the optimal treatment strategy for these disorders.
Two patients with guanidinoacetate methyltransferase defect (GAMT-d) were treated with different amounts of Cr and with diet restrictions aimed at reducing endogenous guanidinoacetate (GAA) synthesis. Three patients with arginine:glycine amidinotransferase defect (AGAT-d) were treated with different Cr intakes. The patients' treatments were monitored by means of (1)H- and (31)P-MR spectroscopy.
Cr and PCr replenishment was lower in GAMT-d than in AGAT-d even when GAMT-d therapy was carried out with a very high Cr intake. Cr and especially PCr replenishment became more efficient only when GAA blood values were reduced. Adenosine triphosphate (ATP) was increased in the baseline phosphorous spectrum of GAMT-d, and it returned to a normal value with treatment. Brain pH and brain P(i) showed no significant change in the AGAT-d syndrome and at any Cr intake. However, 1 of the 2 GAMT-d patients manifested a lower brain pH level while consuming the GAA-lowering diet.
AGAT-d treatment needs lower Cr intake than GAMT-d. Cr supplementation in GAMT-d treatment should include diet restrictions aimed at reducing GAA concentration in body fluids. (1)H- and especially (31)P-MR spectroscopy are the ideal tools for monitoring the therapy response to these disorders.
脑肌酸（Cr）缺乏症（BCr-d）是肌酸生物合成和转运的罕见疾病。我们在长期治疗期间，对受Cr合成缺陷影响的儿童大脑中的总Cr（tCr）及其磷酸化部分磷酸肌酸（PCr）进行了连续测量。目的是确定这些疾病的最佳治疗策略。
两名患有胍基乙酸甲基转移酶缺陷（GAMT-d）的患者接受了不同剂量的Cr治疗，并采用饮食限制以减少内源性胍基乙酸（GAA）的合成。三名患有精氨酸：甘氨酸脒基转移酶缺陷（AGAT-d）的患者接受了不同Cr摄入量的治疗。通过（1）H和（31）P磁共振波谱监测患者的治疗情况。
即使GAMT-d患者采用非常高的Cr摄入量进行治疗，其Cr和PCr的补充仍低于AGAT-d患者。只有当血液中GAA值降低时，Cr尤其是PCr的补充才会更有效。GAMT-d患者的基线磷谱中三磷酸腺苷（ATP）升高，治疗后恢复到正常水平。AGAT-d综合征患者在任何Cr摄入量下，脑pH值和脑无机磷（P(i)）均无显著变化。然而，两名GAMT-d患者中有一名在食用降低GAA的饮食时，脑pH值较低。
AGAT-d治疗所需的Cr摄入量低于GAMT-d。GAMT-d治疗中的Cr补充应包括饮食限制，以降低体液中GAA的浓度。（1）H尤其是（31）P磁共振波谱是监测这些疾病治疗反应的理想工具。
