Nasrallah Fahmi, Kraoua Ichraf, Joncquel-Chevalier Curt Marie, Bout Marie-Adelaïde, Taieb Sameh Hadj, Feki Moncef, Khouja Néziha, Briand Gilbert, Kaabachi Naziha
Laboratory of Biochemistry, Rabta Hospital, Jebbari, 1007 Tunis, Tunisia.
Clin Lab. 2012;58(5-6):427-32.
Guanidinoacetate methyltransferase (GAMT) deficiency is a recently described disorder and few cases have been reported to date. As it is a treatable pathology, we seek to contribute to its better understanding, particularly to further elucidate its biochemical diagnosis for early treatment.
The patients, two brothers aged 13 years (P1) and 11 years (P2), have been explored for signs and symptoms suggestive of inborn errors of metabolism. The quantification of creatine (Cr), guanidinoacetate (GAA), and GAMT activity was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
The two brothers presented a similar clinical picture: developmental delay, epilepsy, axial hypotonia, spastic tetraparesis, severe mental and language delay, and autistic behaviour. GAA concentrations were markedly increased in plasma and in urine [2796 and 3342 micromol/mmol creatinine (control range: 4 - 220 micromol/mmol creatinine)/14 and 29 micromol/L (control range: 0.35 - 1.8 micromol/L), respectively] while plasma and urine creatine concentrations were at the lower normal range limit. Activity of GAMT in lymphoblasts was extremely reduced (< 0.01 nmol/mg protein/hour) compared to healthy subjects. GAMT activity was found to be intermediary in patients' parents.
It appears that the clinical picture is heterogeneous but should be considered as potential signs of creatine metabolism disorders, however, the biochemical diagnosis is reliable as the enzyme activity is zero in most cases. To date, it is still too early to establish correlations between symptoms and biochemical profile. However, the identification of additional cases of GAMT deficiency should help elucidate such relationships and the progress of patients treated with creatine in conjunction with ornithine supplementation.
胍乙酸甲基转移酶（GAMT）缺乏症是一种最近才被描述的疾病，迄今为止报道的病例很少。由于它是一种可治疗的疾病，我们旨在促进对其更好的理解，特别是进一步阐明其生化诊断以实现早期治疗。
对两名年龄分别为13岁（P1）和11岁（P2）的兄弟进行了检查，以寻找提示先天性代谢缺陷的体征和症状。通过液相色谱 - 串联质谱法（LC-MS/MS）对肌酸（Cr）、胍乙酸（GAA）和GAMT活性进行定量分析。
两兄弟表现出相似的临床症状：发育迟缓、癫痫、轴性肌张力减退、痉挛性四肢瘫、严重的智力和语言发育迟缓以及自闭症行为。血浆和尿液中的GAA浓度显著升高[分别为2796和3342微摩尔/毫摩尔肌酐（对照范围：4 - 220微摩尔/毫摩尔肌酐）/14和29微摩尔/升（对照范围：0.35 - 1.8微摩尔/升）]，而血浆和尿液中的肌酸浓度处于正常范围下限。与健康受试者相比，淋巴细胞中的GAMT活性极低（<0.01纳摩尔/毫克蛋白质/小时）。在患者父母中发现GAMT活性处于中间水平。
看来临床症状是异质性的，但应被视为肌酸代谢紊乱的潜在体征，然而，生化诊断是可靠的，因为在大多数情况下酶活性为零。迄今为止，建立症状与生化特征之间的相关性仍为时过早。然而，识别更多GAMT缺乏症病例应有助于阐明此类关系以及联合补充鸟氨酸进行肌酸治疗的患者的病情进展。
