Yamamoto Akiyo, Fukumura Shinobu, Habata Yumi, Miyamoto Sachiko, Nakashima Mitsuko, Takashima Shigeo, Kawasaki Yukihiko, Shimozawa Nobuyuki, Saitsu Hirotomo
Sapporo Medical University School of Medicine, Sapporo, Japan.
Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan.
Child Neurol Open. 2021 Oct 11;8:2329048X211048613. doi: 10.1177/2329048X211048613. eCollection 2021 Jan-Dec.
D-bifunctional protein (DBP) deficiency is a peroxisomal disorder with a high degree of phenotypic heterogeneity. Some patients with DBP deficiency develop progressive leukodystrophy in childhood. We report a 6-year-old boy with moderate hearing loss who presented with developmental regression. Brain magnetic resonance imaging demonstrated progressive leukodystrophy. However, very long chain fatty acids (VLCFAs) in the plasma were at normal levels. Whole-exome sequencing revealed compound heterozygous variants in (NM_000414.3:c.[350A > T];[394C > T], p.[[Asp117Val]];[[Arg132Trp]]). The c.394C > T variant has been identified in patients with DBP deficiency and is classified as likely pathogenic, while the c.350A > T variant was novel and classified as uncertain significance. Although one of the two variants was classified as uncertain significance, an accumulation of phytanic and pristanic acids was identified in the patient, confirming type III DBP deficiency. DBP deficiency should be considered as a diagnosis in children with progressive leukodystrophy and hearing loss even if VLCFAs are within normal levels.
D-双功能蛋白（DBP）缺乏症是一种具有高度表型异质性的过氧化物酶体疾病。一些DBP缺乏症患者在儿童期会发展为进行性脑白质营养不良。我们报告了一名6岁中度听力损失男孩，他出现了发育倒退。脑部磁共振成像显示为进行性脑白质营养不良。然而，血浆中的极长链脂肪酸（VLCFA）水平正常。全外显子测序揭示了（NM_000414.3:c.[350A＞T]；[394C＞T]，p.[[Asp117Val]]；[[Arg132Trp]]）中的复合杂合变体。c.394C＞T变体已在DBP缺乏症患者中被鉴定出，被分类为可能致病，而c.350A＞T变体是新发现的，分类为意义不明确。尽管这两个变体之一被分类为意义不明确，但在该患者中鉴定出植烷酸和降植烷酸的积累，证实为III型DBP缺乏症。即使VLCFA水平正常，对于患有进行性脑白质营养不良和听力损失的儿童，也应考虑诊断为DBP缺乏症。
