2026-07-27 | PATHOPHYSIOLOGICAL, DIAGNOSTIC, AND THERAPEUTIC INSIGHTS INTO ADRENOLEUKODYSTROPHY AND THE ROLE OF NURSING IN COMPREHENSIVE CARE: A LITERATURE REVIEW
Adrenoleukodystrophy (ALD) is a rare, progressive genetic disorder resulting from mutations in the ABCD1 gene, located on the X chromosome, which impair the metabolism of very-long-chain fatty acids (VLCFAs), leading to adrenal dysfunction and neurodegeneration. Given the pathophysiological complexity and therapeutic limitations of the disease, this study aimed to compile and analyze the main scientific evidence regarding the pathophysiological, diagnostic, and therapeutic aspects of ALD, as well as to highlight the importance of nursing in providing comprehensive and palliative care to affected patients. This is an integrative literature review conducted in the PubMed and Virtual Health Library (BVS) databases, using controlled descriptors combined with Boolean operators. Fourteen studies published between 2020 and 2025 were included and analyzed according to the PRISMA protocol. The results show that early diagnosis is possible through spectroscopic techniques, such as liquid chromatography coupled with mass spectrometry (LC-MS), which allow for the identification of the ALD biomarker. Neonatal screening is also essential for a favorable prognosis, enabling early interventions such as hematopoietic stem cell transplantation. New experimental therapies, such as the use of nervonic acid and N-acetylcysteine, show promise. The role of nursing is highlighted as essential in comprehensive care, especially in the implementation of palliative care practices centered on the dignity, comfort, and well-being of the patient and their family. It is concluded that scientific advances and a multidisciplinary approach are indispensable for the effective management of ALD, with nursing playing a central role in coordinating care and providing humanized support.
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2026-07-18 | The complex lipidome as a driver of tissue-specific pathology in adrenoleukodystrophy.
X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal disorder caused by pathogenic variants in the ABCD1 gene, encoding a peroxisomal membrane transporter required for the import of very-long-chain fatty acids (VLCFA) into peroxisomes for degradation. ABCD1 deficiency leads to VLCFA accumulation in plasma and tissues. The resulting disease has a highly variable clinical presentation. In males, this manifests as cerebral demyelination, progressive myelopathy, and adrenal insufficiency, alone or in combination. Women predominantly develop myelopathy, while cerebral disease and adrenal insufficiency are rare, occurring almost exclusively in cases of extreme X-inactivation skewing toward the mutant allele. The lipid-mediated mechanisms linking VLCFA accumulation to tissue-specific pathology remain incompletely understood. Here, we review evidence that VLCFA-containing complex lipids, rather than free VLCFAs alone, are central mediators of tissue-specific pathology in ALD and discuss the therapeutic implications of this lipid-centric perspective. VLCFAs are incorporated into a broad range of complex lipids, including phosphatidylcholines, lysophosphatidylcholines, cholesterol esters, triacylglycerols, sphingomyelins, ceramides, and plasmalogens. The degree of lipid dysregulation increases with acyl chain length and saturation. VLCFA-containing lipid species correlate with disease severity across all clinical phenotypes. In the brain, VLCFA-containing phosphatidylcholines accumulate before demyelination onset, cholesterol ester accumulation is associated with neuroinflammatory cascades, and plasmalogen depletion reflects early oxidative damage. In the spinal cord, VLCFA-containing myelin lipids are associated with non-inflammatory axonopathy, mitochondrial dysfunction, and microglial phagocytic activation. In the adrenal gland, VLCFA accumulation in cholesterol ester-rich lipid droplets impairs ACTH receptor signaling and sequesters cholesterol from steroidogenic pathways. Enzymatic regulators of VLCFA homeostasis, including ELOVL1, SCD1, and the omega-oxidation enzymes CYP4F2 and CYP4F3B, are potential therapeutic targets for substrate reduction. Plasma VLCFA-lipid profiles correlate with disease severity across all affected tissues, positioning lipidomic profiling as a potential clinical instrument for risk stratification and treatment monitoring. Secondary lipid mediators amplify primary VLCFA toxicity through distinct, cell-type-specific pathways. The near-exclusive occurrence of cerebral ALD and adrenal insufficiency in women with extreme X-inactivation skewing suggests that partial reduction of the VLCFA lipid burden, rather than complete normalization, may be sufficient to prevent severe disease manifestations. This has direct implications for substrate-reduction therapy development.
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2026-06-25 | Peroxisomal disorders - incidences in Sweden.
Incidence calculations are crucial for understanding rare disorders, improving healthcare, and public health planning. Our study presents the incidence of peroxisomal disorders in Sweden. All patients diagnosed between 1985 and 2024 at the two existing laboratories, which determine very long-chain fatty acids (VLCFA), phytanic, pristanic, and L-pipecolic acid in plasma, and plasmalogens in erythrocytes, were included in the study. Specifically, the incidence of X-linked adrenoleukodystrophy (X-ALD) is essential for evaluating its inclusion in the national neonatal screening for inborn diseases. Since the incidence of these disorders remained almost constant over the last 20 years of the study, these data were used for calculations. The incidence for the entire cohort (2005-2024) was 1:29,100, excluding female carriers of X-ALD. The most common subgroup was hemizygous X-ALD, with an incidence of 1:65,100, followed by peroxisomal biogenesis disorders (PBDs; Zellweger spectrum disorders) at 1:73,800. These incidences align with other estimates for clinically detected patients, but not for X-ALD detected through neonatal screening, where the incidence is at least three times higher. This discrepancy is partly explained by the discovery of genetic variants of uncertain significance. Over the years, the age at diagnosis and survival time for PBDs have increased, indicating heightened awareness of attenuated forms and improved supportive treatment.
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2026-06-07 | Successful treatment of abnormal sensation associated with restless legs syndrome in adrenoleukodystrophy using Gunggwijohyeoleum-Jeilgagam: A case report.
Adrenoleukodystrophy (ALD) is a rare neurodegenerative disorder frequently associated with restless legs syndrome (RLS), particularly in patients with the adrenomyeloneuropathy (AMN) phenotype. RLS can markedly aggravate abnormal sensations, insomnia, and gait dysfunction; however, conventional treatments, such as dopamine agonists or iron supplementation, are often ineffective or inappropriate, especially in patients without iron deficiency. Herein, we report the clinical effects of herbal medicines in a patient with ALD-associated refractory RLS. A 50-year-old Asian man with genetically confirmed AMN-type ALD presented with a 10-year history of persistent tingling and discomfort in both lower extremities, severe RLS, insomnia, and progressive gait impairment. Despite treatment with baclofen and pramipexole, his symptoms remained refractory, with an International Restless Legs Syndrome Rating Scale (IRLS) score of 31, a Short Physical Performance Battery (SPPB) score of 4, and sleep duration limited to 2-3 h per night. The serum ferritin level was 140 μg/L, indicating adequate iron stores. Based on Korean medicine (KM) pattern identification, the herbal prescription Gunggwijohyeoleum-Jeilgagam (GJG) was administered for 21 days. Following treatment, the IRLS score decreased from 31 to 13, falling below the threshold for severe RLS, while the SPPB score improved from 4 to 6. The sleep duration increased to 5 h, and these improvements were maintained for 5 months after discontinuation without recurrence. GJG demonstrated potential benefit in alleviating refractory RLS-associated abnormal sensations and improving physical function in a patient with ALD. This case suggests that KM may represent a complementary therapeutic option for chronic sensory, sleep, and functional impairments in neurodegenerative disorders when conventional treatments are insufficient.
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2026-06-05 | Peroxisomal ABCD1 deficiency in mice drives Th1 bias through 25-HC-LXR signaling in CD4+ T cells.
X-linked adrenoleukodystrophy (X-ALD) is driven by ABCD1 dysfunction, causing very-long-chain fatty acid (VLCFA) accumulation and cerebral inflammation, yet the role of T cells in X-ALD remains unclear. Here, we show that Abcd1-deficient CD4+ T cells exhibit a strong Th1 bias, producing more IFN-γ and less IL-10 under antigen-specific immunization in vivo and Th1-polarizing conditions in vitro. Transcriptional profiling revealed early induction of Ifng and Tbx21 (T-bet) and late repression of Prdm1 (Blimp-1), indicating Blimp-1-dependent derepression of IFN-γ and reduced IL-10. Mechanistically, liver X receptor (LXR) signaling was markedly amplified, evidenced by upregulation of Abca1, Srebf1, and the oxysterol 25-hydroxycholesterol (25-HC), driven by increased Ch25h. Pharmacological modulation validated this axis: the LXR antagonist SR9238 restored Blimp-1 and IL-10 while reducing IFN-γ, whereas the LXR agonist T0901317 and exogenous 25-HC recapitulated the Abcd1-deficient phenotype. Thus, 25-HC-LXR signaling suppresses Blimp-1, enforcing Th1 polarization in Abcd1-deficient CD4+ T cells. These findings define an immunometabolic link between peroxisomal lipid metabolism and T cell differentiation and highlight the 25-HC-LXR-Blimp-1 axis as a mechanistic link regulating CD4+ T-cell polarization, with potential relevance to X-ALD-associated neuroinflammation.
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