Clinical, neuroimaging, biochemical, and genetic features in six Chinese patients with Adrenomyeloneuropathy

Abstract

Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison’s disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions

“…Signal changes involving pyramidal tracts that extend upwards into the white matter of the centrum semiovale indicate cerebral involvement. MRI of the spinal cord shows non-specific atrophy without any signal changes ( 51 ). There is no specific treatment for AMN apart from the symptomatic management of spasticity and bladder functions.…”

Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders

“…In addition to myeloneuropathy, around 80% of all male X-ALD patients develop adrenocortical insufficiency ( Dubey et al, 2005 ). Symptomatology includes progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, a baldness pattern and increased skin pigmentation, clinical signs that are usually progressive over decades ( Li et al, 2019 ).…”