Misleading behavioural phenotype with adenylosuccinate lyase deficiency
Misleading behavioural phenotype with adenylosuccinate lyase deficiency
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DOI：
10.1038/ejhg.2008.174
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发表时间：
2009-01-01
影响因子：
5.2
通讯作者：
Bahi-Buisson, Nadia
中科院分区：
文献类型：
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作者：
Gitiaux, Cyril;Ceballos-Picot, Irene;Bahi-Buisson, Nadia
腺苷琥珀酸裂解酶缺乏症是一种罕见的常染色体嘌呤合成疾病，其结果是在体液中积累琥珀酰嘌呤。腺苷琥珀酸裂解酶缺乏症患者表现为智力迟钝、癫痫和自闭症特征的可变组合，通常在使用Bratton-Marshall试验进行不明原因脑病筛查时发现，该试验显示琥珀酰氨基咪唑甲酰胺核糖体（SAICAr）的排泄。在这里，我们报告了两个年龄分别为11岁和12岁的姐妹，她们表现出全面发育迟缓、运动失用症、严重的语言缺陷、癫痫发作和行为特征，这些特征包括过度大笑、非常快乐的性格、多动、注意力持续时间短、用嘴接触物体、发脾气和刻板的动作，这些行为特征都模仿了天使人综合症。两例患者均出现琥珀酸腺苷/SAICAr比值升高1.6，并在ADSL基因第6外显子出现新的纯合错义突变（C . 674t >C; p.Met225Thr）。我们认为这些临床特征可能是腺苷琥珀酸裂解酶缺乏症的新表现。在此观察的基础上，虽然腺苷琥珀酸裂解酶缺乏症是一种罕见的疾病，但在有智力迟钝和行为特征提示Angelman综合征的患者中，应考虑这种诊断。
Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton-Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical features might be a new presentation of adenylosuccinate lyase deficiency. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with mental retardation and a behavioural profile suggestive of Angelman syndrome.