Battini Roberta, Alessandrì M Grazia, Casalini Claudia, Casarano Manuela, Tosetti Michela, Cioni Giovanni
Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Viale del Tirreno 331, Calambrone, 56128, Pisa, Italy.
Department of Developmental Neuroscience, MRI Laboratory, IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy.
Orphanet J Rare Dis. 2017 Feb 2;12(1):21. doi: 10.1186/s13023-017-0577-5.
Arginine:glycine amidinotransferase deficiency (AGAT-d) is a very rare inborn error of creatine synthesis mainly characterized by absence of brain Creatine (Cr) peak, intellectual disability, severe language impairment and behavioural disorder and susceptible to supplementary Cr treatment per os. Serial examinations by magnetic resonance spectroscopy are required to evaluate Cr recovery in brain during treatment of high doses of Cr per os, which have been proved beneficial and effective in treating main clinical symptoms. A long term study with detailed reports on clinical, neurochemical and neuropsychological outcomes of the first Italian patients affected by AGAT-d here reported can represent a landmark in management of this disorder thus enhancing medical knowledge and clinical practice.
We have evaluated the long term effects of Cr supplementation management in four Italian patients affected by AGAT-d, correlating specific treatments with serial clinical, biochemical and magnetic resonance spectroscopy examinations as well as the neuropsychological outcome by standardized developmental scales. Consecutive MRS examinations have confirmed that Cr depletion in AGAT-d patients is reversible under Cr supplementation. Cr treatment is considered safe and well tolerated but side effects, including weight gain and kidney stones, have been reported.
Early treatment prevents adverse developmental outcome, while patients diagnosed and treated at an older age showed partial but significant cognitive recovery with clear improvements in adaptive functioning.
精氨酸：甘氨酸脒基转移酶缺乏症（AGAT-d）是一种非常罕见的先天性肌酸合成障碍，主要特征为脑内肌酸（Cr）峰缺失、智力残疾、严重语言障碍和行为障碍，口服补充肌酸治疗有效。在口服高剂量肌酸治疗期间，需要通过磁共振波谱进行系列检查，以评估脑内肌酸的恢复情况，已证实这对治疗主要临床症状有益且有效。本文报道了一项针对首批意大利AGAT-d患者的长期研究，详细报告了其临床、神经化学和神经心理学结果，这可能成为该疾病管理的一个里程碑，从而增进医学知识和临床实践。
我们评估了补充肌酸治疗对四名意大利AGAT-d患者的长期影响，将特定治疗与系列临床、生化和磁共振波谱检查以及通过标准化发育量表评估的神经心理学结果相关联。连续的磁共振波谱检查证实，在补充肌酸的情况下，AGAT-d患者的肌酸消耗是可逆的。肌酸治疗被认为是安全且耐受性良好的，但已报告有包括体重增加和肾结石在内的副作用。
早期治疗可预防不良发育结局，而在较大年龄才确诊和治疗的患者显示出部分但显著的认知恢复，适应性功能有明显改善。
