Chiplunkar Shwetha, Bindu Parayil Sankaran, Nagappa Madhu, Panikulam Bobby Baby, Arvinda Hanumanthapura R, Govindaraj Periyasamy, Srinivas Bharath M M, Gayathri Narayanappa, Jessiena Ponmalar J N, Mathuranath Pavagada S, Sinha Sanjib, Taly Arun B
Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Neuromuscular Laboratory-Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Metab Brain Dis. 2017 Aug;32(4):967-970. doi: 10.1007/s11011-017-0005-5. Epub 2017 Apr 3.
Reports on magnetic resonance imaging findings in patients with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency, an autosomal recessive disorder caused by mutations in the acyl-Coenzyme A dehydrogenase (ACADS), are limited. Many asymptomatic carriers of ACAD variants have also been described necessitating careful evaluation of clinical and biochemical findings for an accurate diagnosis. Here we report a an infant with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency diagnosed based on the characteristic biochemical findings and confirmed by genetic testing. He presented with refractory seizures and neuro regression at 4 months of age. His metabolic work up revealed elevated butyryl carnitine in plasma and ethyl malonic acid in urine. Magnetic resonance imaging of the brain showed cortical and basal ganglia signal changes with cortical swelling. Serial scans showed progression of the lesions resulting in cystic leukomalacia with brain atrophy. Exome sequencing revealed a novel homozygous nonsense variation, c.1146C > G (p.Y382Ter) in exon ten of ACADS which was further validated by Sanger sequencing. Both parents were heterozygous carriers. Follow up at 15 months showed gross psychomotor retardation and refractory seizures despite being on optimal doses of anti-epileptic medications, carnitine and multivitamin supplementation. This report expands the phenotypic and genotypic spectrum of SCAD deficiency.
关于短链酰基辅酶A脱氢酶（SCAD）缺乏症患者的磁共振成像结果的报告有限，SCAD缺乏症是一种由酰基辅酶A脱氢酶（ACADS）突变引起的常染色体隐性疾病。也有许多ACAD变异的无症状携带者被描述，这就需要对临床和生化检查结果进行仔细评估以做出准确诊断。在此，我们报告一名基于特征性生化检查结果诊断为短链酰基辅酶A脱氢酶（SCAD）缺乏症并经基因检测证实的婴儿。他在4个月大时出现难治性癫痫发作和神经功能倒退。他的代谢检查显示血浆中丁酰肉碱升高，尿液中乙基丙二酸升高。脑部磁共振成像显示皮质和基底神经节信号改变以及皮质肿胀。系列扫描显示病变进展，导致囊性脑白质软化和脑萎缩。外显子组测序揭示了ACADS外显子10中一个新的纯合无义变异，即c.1146C>G（p.Y382Ter），该变异经桑格测序进一步验证。父母双方均为杂合子携带者。15个月时的随访显示，尽管使用了最佳剂量的抗癫痫药物、肉碱和多种维生素补充剂，患儿仍存在严重的精神运动发育迟缓及难治性癫痫发作。本报告扩展了SCAD缺乏症的表型和基因型谱。
