Two cases of X-linked adrenoleukodystrophy presenting with Addison′s disease as the initial manifestation and analysis of novel ABCD1 variants
10.3760/cma.j.cn112138-20250515-00280
- VernacularTitle:以Addison病为首发表现的X连锁肾上腺脑白质营养不良2例及ABCD1基因新变异分析
- Author:
Yaqi YIN
1
;
Liqin LI
;
Yu CHENG
;
Li ZANG
;
Weijun GU
;
Zhaohui LYU
;
Yiming MU
Author Information
1. 解放军总医院第一医学中心内分泌科，北京 100039
- Publication Type:Journal Article
- Keywords:
Adrenoleukodystrophy;
Adrenal insufficiency;
Very long-chain fatty acids;
Addison′s disease;
ABCD1 gene
- From:
Chinese Journal of Internal Medicine
2025;64(9):861-867
- CountryChina
- Language:Chinese
-
Abstract:
Clinical data of two patients with X-linked adrenoleukodystrophy (X-ALD) initially presenting as Addison′s disease were collected from the Department of Endocrinology, First Medical Center of Chinese PLA General Hospital. Relevant medical history, clinical features, laboratory tests, and genetic results were analyzed. The two male patients, aged 7 years (case 1) and 15 years (case 2), initially presented with generalized skin hyperpigmentation, without any family history of similar disorders. Both had normal growth and development, and adrenal CT and brain MRI revealed no significant abnormalities. Elevated very long-chain fatty acid (VLCFA) levels were detected. Genetic analyses identified a maternally inherited missense mutation (c.830G>A, p.Gly277Glu) in the ATP-binding cassette subfamily D member 1 (ABCD1) gene in case 1, and a missense mutation (c.1499G>T, p.Gly500Val) in case 2. Protein structural predictions indicated both mutations as potentially damaging or damaging, and both were classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria (PM1/PM2/PP3_Moderate and PM2/PP3_Moderate/PM6, respectively), supporting their correlation with the clinical phenotype. Clinicians should maintain vigilance for X-ALD in male patients presenting with Addison′s disease, and combined VLCFA and genetic testing can effectively prevent misdiagnosis or delayed diagnosis.
