'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'.
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'.
复制标题
“琥珀酸半醛脱氢酶缺乏症：20 年随访中青少年患者的表型演变”。
DOI：
10.1111/j.1469-8749.2008.03116.x
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发表时间：
2008
影响因子：
3.8
通讯作者：
Gibson,KMichael
中科院分区：
文献类型：
--
作者：
Crutchfield,SusanR;Haas,RichardH;Nyhan,WilliamL;Gibson,KMichael
SIR-琥珀酸半醛脱氢酶(SSADH；乙醛脱氢酶5a1，Aldh5a1；OMIM 271980,610045)缺乏症是γ-氨基丁酸(GABa)代谢最常见的疾病，其中两种神经活性物质(GABa和γ-羟丁酸[GHb])积聚(图1)。1、2临床表现为静止性脑病，包括全身性发育迟缓、低眼压、共济失调、言语发育不良或缺失、睡眠障碍和癫痫发作。2由于SSADH缺乏症缺乏其他威胁生命的器官和氨基酸疾病的常见伴随症状(高氨血症、低血糖、代谢性酸中毒)，患者的寿命不会被缩短，父母对疾病表型随年龄的演变有现实的担忧。GABA和GHB的累积是SSADH缺乏症的独特特征，它们具有病理生理学意义。GABA是哺乳动物中的主要抑制性递质，有许多受体系统，这些受体的变化在Aldh5a1−/−小鼠和患者中都有记录。3-6对Aldh5a1−/−小鼠胚胎的代谢研究表明，早在E10(胚胎生命第10天)，GABA和GHb的含量就显著增加，这是因为GABA在发育过程中是兴奋的，可能使神经回路倾向于过度兴奋状态。7GHb也有自己的受体系统，它的积累可能会继而增加GABA，同时加剧GABA对不同受体的影响。8最近，通过应用[11C]氟马西尼结合和经颅磁刺激的研究，发现SSADH缺陷患者存在GABA(A)和GABA(B)受体异常。4、5我们报道了一例最早诊断为SSADH缺乏症的患者的病史和随访。
SIR–Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5a1, Aldh5a1; OMIM 271980, 610045) deficiency is the most prevalent disorder of γ-aminobutyrate (GABA) metabolism, and one in which two neuroactive compounds (GABA and γ-hydroxybutyrate [GHB]) accumulate (Fig. 1). 1, 2 The clinical phenotype is that of a static encephalopathy, including global delay in development, hypotonia, ataxia, poorly-developed or absent speech, sleep disturbance, and seizures. 2 Since SSADH deficiency lacks the usual concomitants (hyperammonemia, hypoglycemia, metabolic acidosis) of other life-threatening organic and amino acid disorders, the lifespan of patients is not thought to be truncated, and parents have realistic concerns as to the evolution of the disease phenotype with age.Accumulation of GABA and GHB are unique features of SSADH deficiency, and they have pathophysiological implications. GABA, the main inhibitory transmitter in mammals, has a number of receptor systems, and alterations of these receptors have been documented both in Aldh5a1−/− mice and in patients. 3-6 Metabolic studies in Aldh5a1−/− murine embryos have revealed significant increases in both GABA and GHB as early as E10 (embryo day of life 10), which is of interest since GABA is excitatory during development and might predispose neural circuity to a hyperexcitatory state. 7 GHB also has its own receptor systems, and its accumulation may increase GABA secondarily while exacerbating the effects of GABA on different receptors. 8 Recently, GABA (A) and GABA (B) receptor abnormalities have been suggested in SSADH-deficient patients through studies employing [11C] flumazenil binding and transcranial magnetic stimulation. 4, 5 Here we report the case history and follow-up for one of the earliest-diagnosed patients with SSADH deficiency.