肾上腺素肌营养不良（ALD）|症状和原因
What causes ALD?
ALD is an X-linked recessive condition caused by a mutation in theABCD1gene on the X chromosome. Because a female has two X chromosomes, if she inherits the faulty gene, then she still has another X chromosome to offset the mutation. However, because males only have one X chromosome, the gene abnormality causes the disease.
每次怀孕时，女性ALD携带者都有25％（四分之一）有载女女儿的机会，而有25％（1％的4）百分之4％的儿子患有这种疾病。
What are the symptoms of ALD?
Boys with cerebral adrenoleukodystrophy usually begin showing symptoms between the ages of 4 and 10. The most common symptoms include:
- behavioral problems
- 提取或侵略
- 记忆力不佳
- poor school performance
- 难以阅读，写作和理解语音
随着病情的进展，脑ALD的其他体征和症状可能包括：
- 视力问题
- seizures
- difficulty swallowing
- 耳聋
- poor coordination
- 无法说话或回应
没有治疗，ALD会迅速发展，通常会在几年内导致植物性状态或死亡。
肾上腺素肌营养不良（ALD）|诊断和治疗
如何诊断肾上腺素肌营养不良？
Early diagnosis of cerebral ALD is critical, because there is a narrow window in which the condition can be treated. Once the disease progresses, there is no way to replace the lost myelin or reverse the neurological damage already done.
诊断测试
没有家族史，大多数妇女都不知道自己是ALD的载体。结果，他们的儿子经常被误诊，症状很容易被误认为行为或发育问题。
When a clinician suspects ALD, they will perform two tests — a磁共振成像（MRI）扫描以确定是否对脑组织有损害和血液测试，以测量非常长的链脂肪酸的浓度，这些链脂肪酸的浓度在ALD的男性中升高。
Genetic testing
基因检测可以鉴定导致ALD的缺陷基因。它还可以准确地识别有ALD的家庭成员 - 尚未表现出症状的载体和男孩。
Newborn screening
A newborn screening test, which was added to the United States Recommended Uniform Newborn Screening Panel in 2016 but currently is available in only a handful of states, detects elevated very long chain fatty acid levels in the blood, a clear indicator of ALD. With newborn screening, boys at risk can be identified and treated early.
What are the treatment options for ALD?
Stem cell transplant
脑ALD唯一有效的治疗选择是stem cell transplant，患者从遗传匹配的供体中接收血干细胞的过程。目的是提供健康的干细胞，可产生ALD男孩缺乏蛋白质的蛋白质。
Prior to the stem cell transplant, there is an intensive process to prepare for treatment. This involves using chemotherapy to prepare the body to receive the donor cells. Although a donor stem cell transplant has been shown to halt the progression of ALD, it has its own set of challenges and risks:
- It can be difficult to find a donor match that has a similar or identical genetic makeup
- There is a high risk of infection, because the immune system is strongly inhibited to allow the recipient’s body to accept the transplanted new stem cells.
- 移植后，这种情况继续进行六到18个月，因此早期治疗至关重要。
- For symptomatic boys, a transplant can in some cases be associated with a rapidly advanced condition.
基因治疗for ALD
基因治疗is being studied as a potential treatment for cerebral ALD. A临床试验在Dana-Farber/波士顿儿童癌症和血液疾病中心使用无症状ALD男孩的实验方法。他们自己的血干细胞被去除，用载体在实验室中处理，这是一种非感染病毒，用于获取生产ALD蛋白的基因（ABCD1gene) into the cell. The cells containing the vector, carrying the new gene, are then given back to the patient by an intravenous (IV) infusion. When these new cells grow, divide and make new cells in the body, they will have theABCD1gene and be able to break down the very long chain fatty acids that cause the serious neurological symptoms of ALD.
尽管仍在实验中，但这种方法的优点是没有必要寻找捐赠者，因此没有人有与身体作斗争的风险（称为“嫁接 - 宿主疾病”），因此无需强大的风险免疫抑制药物。
了解更多有关Gene Therapy Program.