PDF(Pubmed)
Abstract：
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene leading to very long chain fatty acid (VLCFA) accumulation. The disease demonstrates a spectrum of phenotypes including adrenomyeloneuropathy (AMN). We aimed to identify the genetic basis of disease in a patient presenting with AMN features in order to confirm the diagnosis, expand genetic knowledge of ABCD1 mutations, and elucidate potential genotype-phenotype associations to inform management.
METHODS: A 29-year-old male presented with a 4-year history of progressive spastic paraplegia, weakness of lower limbs, fecal incontinence, sexual dysfunction, hyperreflexia, and positive Babinski and Chaddock signs.
METHODS: Neuroimaging revealed brain white matter changes and spinal cord thinning. Significantly elevated levels of hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) suggested very long chain fatty acids (VLCFA) metabolism disruption. Genetic testing identified a novel hemizygous ABCD1 mutation c.249dupC (p.F83fs). These findings confirmed a diagnosis of X-linked ALD with an AMN phenotype.
METHODS: The patient received dietary counseling to limit VLCFA intake. Monitoring for adrenal insufficiency and consideration of Lorenzo\'s oil were advised. Genetic counseling and testing were offered to at-risk relatives.
RESULTS: At present, the patient continues to experience progressive paraplegia. Adrenal function remains normal thus far without steroid replacement. Family members have undergone predictive testing.
CONCLUSIONS: This case expands the known mutation spectrum of ABCD1-linked X-ALD, providing insight into potential genotype-phenotype correlations. A thoughtful diagnostic approach integrating clinical, biochemical and genetic data facilitated diagnosis. Findings enabled genetic counseling for at-risk relatives regarding this X-linked disorder.
METHODS: A 29-year-old male presented with a 4-year history of progressive spastic paraplegia, weakness of lower limbs, fecal incontinence, sexual dysfunction, hyperreflexia, and positive Babinski and Chaddock signs.
METHODS: Neuroimaging revealed brain white matter changes and spinal cord thinning. Significantly elevated levels of hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) suggested very long chain fatty acids (VLCFA) metabolism disruption. Genetic testing identified a novel hemizygous ABCD1 mutation c.249dupC (p.F83fs). These findings confirmed a diagnosis of X-linked ALD with an AMN phenotype.
METHODS: The patient received dietary counseling to limit VLCFA intake. Monitoring for adrenal insufficiency and consideration of Lorenzo\'s oil were advised. Genetic counseling and testing were offered to at-risk relatives.
RESULTS: At present, the patient continues to experience progressive paraplegia. Adrenal function remains normal thus far without steroid replacement. Family members have undergone predictive testing.
CONCLUSIONS: This case expands the known mutation spectrum of ABCD1-linked X-ALD, providing insight into potential genotype-phenotype correlations. A thoughtful diagnostic approach integrating clinical, biochemical and genetic data facilitated diagnosis. Findings enabled genetic counseling for at-risk relatives regarding this X-linked disorder.
摘要：
背景：X-连锁肾上腺脑白质营养不良（X-ALD）是由ABCD1基因突变引起的，导致极长链脂肪酸（VLCFA）积累。该疾病表现出一系列表型，包括肾上腺脊髓神经病（AMN）。我们的目的是确定患有AMN特征的患者的疾病的遗传基础，以确认诊断。扩大ABCD1突变的遗传知识，并阐明潜在的基因型-表型关联，以告知管理。
方法：一名29岁男性，有4年的进行性痉挛性截瘫病史，下肢无力，大便失禁,性功能障碍,反射亢进,还有积极的巴宾斯基和查多克标志.
方法：神经影像学显示脑白质改变和脊髓变薄。六烷酸（C26：0）和四烷酸（C24：0）的水平显着升高表明非常长链的脂肪酸（VLCFA）代谢中断。遗传检测确定了一个新的半合子ABCD1突变c.249dupC（p。F83fs)。这些发现证实了具有AMN表型的X连锁ALD的诊断。
方法：患者接受饮食咨询以限制VLCFA的摄入。建议监测肾上腺功能不全并考虑使用Lorenzo油。向有风险的亲属提供遗传咨询和检测。
结果：目前，患者继续出现进行性截瘫。到目前为止，没有类固醇替代，肾上腺功能仍然正常。家庭成员接受了预测测试。
结论：该案例扩展了ABCD1连接的X-ALD的已知突变谱，深入了解潜在的基因型-表型相关性。一种深思熟虑的诊断方法，整合临床，生化和遗传数据有助于诊断。研究结果为这种X连锁疾病的风险亲属提供了遗传咨询。
方法：一名29岁男性，有4年的进行性痉挛性截瘫病史，下肢无力，大便失禁,性功能障碍,反射亢进,还有积极的巴宾斯基和查多克标志.
方法：神经影像学显示脑白质改变和脊髓变薄。六烷酸（C26：0）和四烷酸（C24：0）的水平显着升高表明非常长链的脂肪酸（VLCFA）代谢中断。遗传检测确定了一个新的半合子ABCD1突变c.249dupC（p。F83fs)。这些发现证实了具有AMN表型的X连锁ALD的诊断。
方法：患者接受饮食咨询以限制VLCFA的摄入。建议监测肾上腺功能不全并考虑使用Lorenzo油。向有风险的亲属提供遗传咨询和检测。
结果：目前，患者继续出现进行性截瘫。到目前为止，没有类固醇替代，肾上腺功能仍然正常。家庭成员接受了预测测试。
结论：该案例扩展了ABCD1连接的X-ALD的已知突变谱，深入了解潜在的基因型-表型相关性。一种深思熟虑的诊断方法，整合临床，生化和遗传数据有助于诊断。研究结果为这种X连锁疾病的风险亲属提供了遗传咨询。
