Rajakumar Hamrish Kumar, Coimbatore Sathyabal Varsha, Nachiappan Revathi, Krishnaswamy Vijayaramanujam Sivakumar
Department of Pediatrics, Government Medical College, Omandurar, Government Estate, Chennai, Tamilnadu, India.
Degener Neurol Neuromuscul Dis. 2024 Jun 17;14:75-83. doi: 10.2147/DNND.S442985. eCollection 2024.
X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.
We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.
ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.
X连锁肾上腺脑白质营养不良（ALD）是一种罕见的遗传性疾病，由ABCD1基因的致病性变异引起，导致过氧化物酶体功能受损和极长链脂肪酸（VLCFA）积累。ALD表现出广泛的神经和肾上腺症状，从儿童脑型肾上腺脑白质营养不良到肾上腺脊髓神经病和肾上腺功能不全。一些地区提供了针对ALD的新生儿筛查（NBS），但其他地区，如印度，仍然缺乏。
我们报告一例10岁患有ALD的男孩，其表现为癫痫发作、进行性肌无力、视力障碍和肾上腺功能不全。尽管进行了对症治疗和饮食调整，疾病仍迅速进展，导致呼吸衰竭并最终死亡。通过分子分析和升高的VLCFA水平确诊。神经影像学显示与ALD一致的特征性白质改变。
ALD是一种无法治愈的毁灭性疾病，强调了通过新生儿筛查和基因检测进行早期检测的重要性。管理策略包括肾上腺激素治疗、基因治疗和同种异体干细胞移植，以及诸如VLCFA正常化等研究性治疗。我们的病例提倡在全球范围内进行NBS和儿科神经学随访，以实现早期干预并改善患者预后。此外，ALD、复发性热性惊厥和不明原因发育迟缓之间的关联值得进一步研究，以更好地了解疾病进展和潜在治疗靶点。
