International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach.
International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach.
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DOI：
10.1212/wnl.0000000000201374
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发表时间：
2022-11-22
期刊：
影响因子：
9.9
通讯作者：
Huffnagel, Irene C.
中科院分区：
文献类型：
--
作者：
Engelen, Marc;Van Ballegoij, Wouter J. C.;Mallack, Eric James;Van Haren, Keith P.;Kohler, Wolfgang;Salsano, Ettore;Van Trotsenburg, A. S. P.;Mochel, Fanny;Sevin, Caroline;Regelmann, Molly O.;Tritos, Nicholas A.;Halper, Alyssa;Lachmann, Robin H.;Davison, James;Raymond, Gerald V.;Lund, Troy C.;Orchard, Paul J.;Kuehl, Joern-Sven;Lindemans, Caroline A.;Caruso, Paul;Turk, Bela Rui;Moser, Ann B.;Vaz, Frederic M.;Ferdinandusse, Sacha;Kemp, Stephan;Fatemi, Ali;Eichler, Florian S.;Huffnagel, Irene C.
ABCD1 基因的致病性变异会导致肾上腺脑白质营养不良 (ALD)，这是一种进行性代谢紊乱，其特征为 3 种核心临床综合征：缓慢进行性脊髓神经病、快速进行性炎性脑白质营养不良（脑 ALD）和原发性肾上腺皮质功能不全。这些综合征并不存在于所有个体中，并且与基因型无关。由于外显率和发病年龄不同，脑 ALD 和肾上腺功能不全需要早期发现和干预，并需要临床监测。新生儿筛查增加了接受观察的症状前个体的数量，但临床监测方案各不相同。我们在 28 名国际 ALD 专家中采用了基于共识的改良德尔菲法，为 ALD 患者的诊断、临床监测和治疗制定了最佳实践建议。我们确定了 39 个离散的共识领域。建议对所有男性患者进行定期监测，以检测肾上腺衰竭的发生和脑酒精性肝病的转变。造血细胞移植 (HCT) 是脑 ALD 的首选治疗方法。该指南满足了全球 ALD 社区的临床需求，因为由于新生儿筛查和新一代测序的可用性提高，总体诊断数量和症状前个体数量不断增加。预测病程的能力较差，可以告知当前的监测间隔，但随着更多数据的出现，仍可能发生变化。这种知识差距应该指导未来的研究，并再次说明医生、研究人员和患者之间的国际合作对于改善护理至关重要。
Pathogenic variants in the ABCD1 gene cause adrenoleukodystrophy (ALD), a progressive metabolic disorder characterized by 3 core clinical syndromes: a slowly progressive myeloneuropathy, a rapidly progressive inflammatory leukodystrophy (cerebral ALD), and primary adrenal insufficiency. These syndromes are not present in all individuals and are not related to genotype. Cerebral ALD and adrenal insufficiency require early detection and intervention and warrant clinical surveillance because of variable penetrance and age at onset. Newborn screening has increased the number of presymptomatic individuals under observation, but clinical surveillance protocols vary. We used a consensus-based modified Delphi approach among 28 international ALD experts to develop best-practice recommendations for diagnosis, clinical surveillance, and treatment of patients with ALD. We identified 39 discrete areas of consensus. Regular monitoring to detect the onset of adrenal failure and conversion to cerebral ALD is recommended in all male patients. Hematopoietic cell transplant (HCT) is the treatment of choice for cerebral ALD. This guideline addresses a clinical need in the ALD community worldwide as the number of overall diagnoses and presymptomatic individuals is increasing because of newborn screening and greater availability of next-generation sequencing. The poor ability to predict the disease course informs current monitoring intervals but remains subject to change as more data emerge. This knowledge gap should direct future research and illustrates once again that international collaboration among physicians, researchers, and patients is essential to improving care.