杂合子丢失
复合杂合度
丙戊酸
医学
二甲双胍
内科学
内分泌学
缺锌(植物性疾病)
脑病
癫痫
结节性硬化
糖尿病
药理学
表型
生物
病理
遗传学
基因
精神科
等位基因
微量营养素
作者
Jonathan Kopel,Amy Grooms,Vadivel Ganapathy,Jeffrey Clothier
标识
DOI:10.1097/ypg.0000000000000269
摘要
SLC13A5/NaCT is a sodium-coupled citrate transporter expressed in the plasma membrane of the liver, testis, and brain. In these tissues, SLC13A5 has important functions in the synthesis of fatty acids, cholesterol, and neurotransmitters. In recent years, patients homozygous for recessive mutations in SLC13A5, known as SLC13A5 deficiency [early infantile epileptic encephalopathy-25 (EIEE-25)], exhibit severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting tooth development. Although the pathogenesis of SLC13A5 deficiency remains not clearly understood, cytoplasmic citrate deficits, decreased energy status in neurons, and citrate-zinc chelation are hypothesized to explain the neurological deficits. However, no study has examined the possibility of specific pharmacological drugs and/or lifestyle changes synergizing with heterozygosity of SLC13A5 deficiency to increase the risk of EIEE-25 clinical phenotype. Here, we report on a heterozygous SLC13A5-deficient patient who demonstrated evidence of pharmaco-synergistic heterozygosity upon administration of metformin, valproic acid, and starvation. The report illustrates the importance of careful consideration of the potential adverse effects of specific pharmacological treatments in patients with heterozygosity for disease-causing recessive mutations in SLC13A5.
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