背景:本文介绍了一个案例研究,该案例研究涉及两名年龄为24岁和31岁的白人男性兄弟姐妹,他们自我报告为乌克兰种族,诊断为肾上腺脊髓神经病变(AMN),与ABCD1基因的一个新的剪接位点突变相关。AMN代表X连锁肾上腺脑白质营养不良(X-ALD)的一种形式,其特征是脊髓和周围神经脱髓鞘。该病例还介绍了乌克兰第一个成人造血干细胞移植(HSCT)治疗肾上腺神经神经病。这种突变的稀有性及其大脑受累和治疗使这种情况值得注意,并强调了报告它对现有医学知识的重要性。
方法:24岁和31岁的患者最初表现出进行性步态障碍,下肢疼痛,和尿失禁,随着年长的兄弟姐妹出现更高级的言语症状,听力,和视力障碍。一项全面的遗传分析确定了ABCD1基因外显子3中一个未报道的剪接位点突变,导致AMN的表现。遗传模式与X连锁隐性传播一致。文章还概述了临床特征,磁共振成像(MRI),和神经传导研究(NCS)的发现。此外,它讨论了家庭中受影响的个体和女性携带者的遗传特征。年轻的兄弟姐妹接受了HSCT,并发纵隔淋巴结和肺结核,增加了成人ALD患者管理的复杂性。
结论:本报告强调了基因检测在诊断和理解罕见遗传病的潜在机制方面的重要性。例如大脑受累的AMN。新的剪接位点突变的鉴定扩展了我们对这种情况的遗传景观的理解。此外,造血干细胞移植过程中遇到的挑战和并发症凸显了成年ALD患者需要谨慎考虑和个性化治疗.
BACKGROUND: This article presents a
case study of two white male siblings of 24 and 31 years of age of self-reported Ukrainian ethnicity diagnosed with adrenomyeloneuropathy (AMN) associated with a novel splice site mutation in the ABCD1 gene. AMN represents a form of X-linked adrenoleukodystrophy (X-ALD) characterized by demyelination of the spinal cord and peripheral nerves. The
case also presents the first adult haematopoietic stem cell transplant (HSCT) for adrenomyeloneuropathy in Ukraine. The rarity of this mutation and its cerebral involvement and the treatment make this
case noteworthy and underscore the significance of reporting it to contribute to the existing medical knowledge.
METHODS: The patients of 24 and 31 years initially exhibited progressive gait disturbance, lower extremity pain, and urinary incontinence, with the older sibling experiencing more advanced symptoms of speech, hearing, and vision disturbances. A comprehensive genetic analysis identified an unreported splice site mutation in exon 3 of the ABCD1 gene, leading to the manifestation of AMN. The inheritance pattern was consistent with X-linked recessive transmission. The article also outlines the clinical features, magnetic resonance imaging (MRI), and nerve conduction study (NCS) findings. Moreover, it discusses the genetic profile of the affected individuals and female carriers within the family. The younger sibling underwent HSCT, which was complicated by mediastinal lymph node and lung tuberculosis, adding to the complexity of managing adult ALD patients.
CONCLUSIONS: This report emphasizes the importance of genetic testing in diagnosing and comprehending the underlying mechanisms of rare genetic disorders, such as AMN with cerebral involvement. The identification of a novel splice site mutation expands our understanding of the genetic landscape of this condition. Additionally, the challenges and complications encountered during the hematopoietic stem cell transplant procedure underscore the need for cautious consideration and personalized approaches in adult ALD patients.