副腎白質ジストロフィー

Adrenoleukodystrophy (ALD) is an X-linked recessive disease caused by defects in the ABCD1 gene, leading to the accumulation of very long-chain fatty acids in the nervous system, adrenal glands, blood and other tissues. Male ALD patients may present with either the severe neurological phenotype of cerebral ALD, characterized by inflammatory demyelination in the white matter and rapid neurological deterioration, or milder forms, such as adrenomyeloneuropathy. We aimed to identify early brain changes in asymptomatic ALD patients prior to the clinical onset of cerebral ALD or adrenomyeloneuropathy by exploratory analysis of multimodal MRI data. Multimodal MRI data-including structural images, diffusion tensor imaging, magnetization transfer imaging and MR spectroscopy-were obtained from asymptomatic ALD patients during regular follow-up MRIs. Longitudinal MRI data were analysed from 12 asymptomatic ALD patients aged 10-18 years who did not develop a cerebral ALD phenotype during our surveillance and from 12 healthy age-matched male controls. Volumetric analyses of brain structures were performed using structural MRI data, as well as region-of-interest measurements on diffusion tensor imaging, magnetization transfer imaging and MR spectroscopy data. Statistical analysis was performed using linear mixed-effects models. Volumetry indicated increased white matter volume in asymptomatic ALD patients. Diffusion tensor imaging analysis revealed increased values of radial and mean diffusivity in the supratentorial white matter. Magnetization transfer saturation values derived from magnetization transfer imaging metrics were increased in the cortical and subcortical grey matter, but not in the white matter. MR spectroscopy showed increased inositol levels in the frontal white matter. Our diffusion tensor imaging and MR spectroscopy data indicate early white matter pathology in adolescent asymptomatic ALD patients. Among these findings, increased white matter volume and, in addition, elevated magnetization transfer saturation values in the grey matter are novel MRI phenotypes associated with asymptomatic ALD. These results suggest that not only white matter but also grey matter can be pathologically altered even before the onset of neurological phenotypes. Multimodal MRI parameters therefore constitute promising biomarkers for the assessment of pre-symptomatic brain tissue alterations in ALD and may be useful in future clinical studies targeting early therapeutic intervention.

Cerebral adrenoleukodystrophy (CALD) is a progressive immune-inflammatory neurologic disease that can be arrested with autologous hematopoietic cell transplant-based gene therapy (GT) or allogeneic hematopoietic cell transplantation (Allo-HCT). We compared transplant types by evaluating changes in two biomarkers, C26:0-lysophosphatidylcholine (C26:0-lysoPC) and neurofilament light chain (NfL), before and 12 months after therapy. Disease severity was quantified by Loes score on MRI. Baseline C26:0-lysoPC was 489 nmol/L for GT recipients and 487 nmol/L for Allo-HCT recipients; it decreased by 6.7% after GT and 48.4% after Allo-HCT (p < 0.0001). Baseline NfL was 17.3 for GT recipients and 35.9 pg/mL for Allo-HCT recipients; it increased by 143% after GT and decreased by 43% after Allo-HCT (p = 0.0006). Loes score progression was greater with GT (+3.0 vs. +1.0 points, p = 0.0134). Multivariate analyses to understand which pre-HCT variable was best associated with disease progression indicated that modality of transplant, GT, was the only significant factor (p = 0.0302).

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is associated with serious clinical consequences. While newborn screening (NBS) could facilitate early identification and timely intervention, its implementation for X-ALD remains controversial due to ethical concerns arising from its X-linked recessive inheritance pattern, particularly regarding female newborns. This study aims to explore the perspectives of healthcare professionals and the general public on NBS for X-ALD in Hong Kong. An online survey with 20 quantitative questions on ethical considerations was conducted from May to August 2024. Among a total of 259 responses, most respondents (99.2%) supported NBS for their male newborns, primarily because it facilitates early diagnosis and effective management. The majority of the respondents were in favor of offering NBS to female newborns, citing potential benefits for the management of adult-onset disease, enhanced family planning and support, and opportunities for extended family screening. However, some respondents expressed concerns regarding (1) psychological stress and anxiety from uncertain disease onset and frequent monitoring; (2) potential genetic discrimination and adverse impact on insurance premiums/coverage; (3) affordability and accessibility of expensive treatments, such as gene therapy; and (4) ethical issues regarding children's "right to an open future", particularly for late-onset female X-ALD. To address these concerns while respecting family autonomy, we propose an opt-in system with clear, balanced information for parents, combined with a three-tier screening algorithm. In summary, while inclusion of X-ALD in Hong Kong's NBS program receives strong community support, targeted measures are needed to mitigate the identified ethical and practical barriers.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. Although the quantification of very long-chain fatty acids (VLCFA) is an old technique implemented to diagnose and monitor, the limited number of experienced clinical biochemists in this field and also the limited availability of technical resources have resulted in scarce reports on the prevalence of X-ALD in developing countries like Brazil. This retrospective cross-sectional study analyzed all records of Brazilian patients diagnosed with X-ALD in LAM/SGM/HCPA from November 1992 to June 2026. Plasma VLCFA levels were analyzed by GC at diagnosis, along with patients' symptoms and their country's geographical origin. This is the largest reported Brazilian cohort (N = 275), comprising the three clinical forms of the disease: Addison disease, adrenomyeloneuropathy and childhood cerebral. Plasma VLCFA levels were consistently elevated across all phenotypes, characterizing the diagnosis together with the clinical manifestations and age. CCALD was primarily characterized by neurodevelopmental regression, seizures, behavioral disturbances, and visual impairment, whereas AMN was mainly associated with progressive myelopathy, and adrenocortical insufficiency was the predominant clinical manifestation in AD. Family history was identified in 43.3% of patients, and the mean diagnostic delay was 2.4 years for CCALD and 7.7 years for AMN, highlighting the importance of early recognition and family screening. Therefore, a detailed description of the patient's clinical presentation is essential for the correct diagnosis and interpretation of biochemical tests. Professionals need to be alert to this disease, given that multidisciplinary care is required.

Adult-onset cerebral adrenoleukodystrophy is potentially treatable but often difficult to recognize before advanced cerebral involvement. Herein, we describe three men with early-stage disease who initially presented with subtle visual complaints rather than subcortical dementia. Targeted neuropsychological testing revealed higher-order visual dysfunction and posterior interhemispheric disconnection signs, including visual-field-dependent reading or naming deficits and dichotic listening abnormalities. Diffusion tensor imaging showed preferential involvement of posterior callosal and visual stream-related white-matter pathways. These findings define a posterior disconnection phenotype of adult-onset cerebral adrenoleukodystrophy and provide a clinically useful framework for early recognition and timely therapeutic consideration of this treatable leukodystrophy.