[Screening and genetic variation analysis of fatty acid oxidation disorder in neonates in Qingdao City].

摘要

OBJECTIVES: To investigate the incidence, genetic mutation characteristics, and prognosis of fatty acid oxidation disorder (FAOD) in neonates in Qingdao. METHODS: Clinical data of neonates diagnosed with FAOD from 2014 to 2023 at the Qingdao Neonatal Disease Screening Center were collected and analyzed to determine the incidence, genotype, and prognosis. RESULTS: Among 562 225 neonates screened, 42 were diagnosed with FAOD across six types, yielding an overall incidence of 1/13 386. Primary carnitine deficiency was the most common (20 cases, 48%), with one case showing growth retardation during follow-up. Medium-chain acyl-CoA dehydrogenase deficiency was identified in 6 cases, all of whom demonstrated normal development during follow-up. Short-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases, with one case exhibiting skin erythema, papules, scaling, and dryness during follow-up. Very-long-chain acyl-CoA dehydrogenase deficiency was diagnosed in 5 cases; during follow-up, one patient died and another experienced recurrent rhabdomyolysis. Short/branched-chain acyl-CoA dehydrogenase deficiency was found in 4 cases, with one case showing language regression during follow-up. Multiple acyl-CoA dehydrogenase deficiency was detected in 2 cases; during follow-up, one patient died and one exhibited delayed motor development. Genetic testing performed on 37 of the 42 patients with FAOD identified a hotspot mutation, c.1400C>G, in the SLC22A5 gene among those with primary carnitine deficiency, whereas no predominant hotspot mutations were detected in other FAOD subtypes. CONCLUSIONS: In Qingdao, primary carnitine deficiency is the most prevalent subtypes of FAOD in neonates, characterized by the hotspot mutation c.1400C>G in the SLC22A5 gene. Except for very-long-chain acyl-CoA dehydrogenase deficiency and multiple acyl-CoA dehydrogenase deficiency, most children with other FAOD subtypes have a favorable prognosis. 目的: 调查青岛市新生儿脂肪酸氧化障碍性疾病（fatty acid oxidation disorder, FAOD）的发病率、基因突变特点和预后。方法: 收集青岛市新生儿疾病筛查中心2014—2023年确诊的FAOD患儿的临床资料，分析FAOD的发病率、基因型和预后。结果: 在562 225例新生儿中，共确诊42例FAOD患儿（6种亚型），总发病率为1/13 386。其中原发性肉碱缺乏症最常见（20例，48%），随访期间1例出现生长发育迟缓;中链酰基辅酶A脱氢酶缺乏症6例，随访期间患儿均发育良好;短链酰基辅酶A脱氢酶缺乏症5例，随访期间1例出现皮肤红斑、丘疹、鳞屑伴干燥;极长链酰基辅酶A脱氢酶缺乏症5例，随访期间1例死亡，1例反复出现横纹肌溶解;短/支链酰基辅酶A脱氢酶缺乏症4例，随访期间1例语言发育倒退;多种酰基辅酶A脱氢酶缺乏症2例，随访期间1例死亡，1例运动发育迟缓。对42例FAOD患儿中的37例行基因检测，结果显示SLC22A5基因c.1400C>G为原发性肉碱缺乏症患儿的热点突变，其余FAOD亚型未检出类似高频热点突变。结论: 青岛市新生儿FAOD以原发性肉碱缺乏症发病率最高，其热点突变为SLC22A5基因c.1400C>G。除极长链酰基辅酶A脱氢酶缺乏症和多种酰基辅酶A脱氢酶缺乏症外，其余亚型患儿大多预后良好。.