Section of Biochemical Genetics, The Children's Hospital of Philadelphia, 34th& Civic blvd. 9S23, Philadelphia, PA 19104, USA.
J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S129-31. doi: 10.1007/s10545-009-9041-6. Epub 2010 Jan 27.
Very-long-chain acyl-coenzyme A (CoA) dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder of fatty acid oxidation. The phenotype of VLCADD is heterogeneous, and patients are typically classified into three categories based upon onset of symptoms and clinical findings. As a result of early diagnosis and treatment, many patients with VLCADD have remained asymptomatic. A general genotype-phenotype correlation has been elicited. A genotype that is associated with residual enzyme activity is more likely to present with an attenuated phenotype. One prevailing mutation, the c.848T>C (p.V283A), has been associated with residual enzyme activity and has been identified in many asymptomatic individuals diagnosed through either newborn or family screening. We present a patient who died as a result of fatal hypoglycemia at 38 h of life before diagnosis of VLCADD could be established by newborn screening. Despite the early onset of the disease, the patient was found to have a missense mutation within the ACADVL gene with a c.848T>C, c.342+1G>C genotype. Genotype alone remains limited in its predictive ability to determine which affected individuals are at risk for fatal complications.
长链酰基辅酶 A 脱氢酶缺乏症（VLCADD）是一种脂肪酸氧化的常染色体隐性遗传病。VLCADD 的表型呈异质性，根据症状和临床发现，患者通常分为三类。由于早期诊断和治疗，许多 VLCADD 患者仍无症状。已经得出了一般的基因型-表型相关性。与残留酶活性相关的基因型更有可能表现出减弱的表型。一个流行的突变，c.848T>C（p.V283A），与残留酶活性相关，并已在许多通过新生儿或家族筛查诊断为无症状的个体中被发现。我们介绍了一位患者，他在 38 小时的生命中因致命性低血糖而死亡，在此之前，新生儿筛查尚未确定 VLCADD 的诊断。尽管疾病早期发病，但该患者在 ACADVL 基因中发现了一个错义突变，基因型为 c.848T>C，c.342+1G>C。基因型单独在预测哪些受影响的个体有致命并发症风险方面仍然存在局限性。
