講演情報
[OE3-2]2つの意義不明バリアントを有する極長鎖アシルCoA脱水素酵素欠損症疑いの乳児の診断における課題
○Tocan Vlad, 島本 太郎, 虫本 雄一, 安部 希, 石井 加奈子, 大賀 正一 (九州大学大学院 医学研究院 成長発達医学分野)
BACKGROUND: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a treatable mitochondrial fatty acid oxidation disorder. In Japan, newborn screening (NBS) by tandem mass spectrometry has feasibly detected VLCAD since 2013. However, physicians and families are often faced with a dilemma when asymptomatic infants are found to have variants with uncertain clinical significance (VUS). CASE REPORT: A twelve-day old male infant was referred to our hospital because of elevated C14:1 levels at the NBS. At his first visit, the infant had normal weight gain and transaminases and creatine kinase (CK) levels. He was a compound heterozygote with two missense VUS (A263T and G476D) in the ACADVL gene. During the first year of life, the infant was closely observed and treated similarly to a definite patient during febrile episodes, when he had slightly elevated CK levels. Sequencing of parental ACADVL and measurements of the infant’s VLCAD activity were performed to establish the pathogeny of the variants. The parents were actively included in the diagnostic process and were repeatedly counseled about the possible clinical course of the child as well as the extended genetic implications for the family. DISCUSSION: The implications of VUS in genes related to inherited metabolic disorders are not easily determined unless a definite metabolic crisis episode occurs, but the very scope of observation and treatment is to prevent such episodes. Available investigative methods must be used to predict the level of pathogeny while parents should be informed about possible clinical courses.