Neurogenetics
Clinical and genetic characteristics of adrenomyeloneuropathy
Liu Taotao, Liu Xiaoli, Wu Jingying, Ni Ruilong, Zhang Mengyuan, Ji Duxin, Zhang Mei, Cao Li
Published 2023-04-08
Cite as Chin J Neurol, 2023, 56(4): 392-403. DOI: 10.3760/cma.j.cn113694-20220824-00640
Abstract
ObjectiveTo summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy (AMN).
MethodsClinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022. Clinical characteristics of AMN patients with different types of gene mutations were compared. Loe score was used to evaluate the severity of white matter demyelinating, and the serum levels of very long-chain fatty acids (VLCFA) in patients with or without white matter demyelinating were compared. The motor function of the AMN patients was assessed using the Expanded Disability Status Scale (EDSS), and the association between EDSS scores and the course of disease was analyzed.
ResultsA total of 23 male patients with onset age of (29.52±9.91) years were included in this study. The first symptom of all patients was abnormal lower extremities, of which 17 patients showed stiffness and weakness in their lower limbs (73.9%, 17/23), and 6 patients showed numbness and pain in both lower limbs (26.1%, 6/23). The occurrence of symptoms was not related to the type of gene mutation. White matter demyelination occurred in 33.3% (7/21) of patients over a disease duration of (7.67±4.46) years. There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group. The EDSS score was positively correlated with the disease duration (r=0.57, P=0.006). Sixteen ABCD1 gene mutations were found in this study, among which c.5_19delinsTCTCCAGG (p.P2Lfs*12) was reported for the first time. Four probands belonging to different families carried the c.1415_1416del (p.Q472Rfs*83) variant.
ConclusionsLower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients, with deterioration of motor function associated with the course of disease. AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes. The c.1415_1416del (p.Q472Rfs*83) mutation is a hot spot mutation of the disease.
Key words:
Adrenoleukodystrophy; Leukoencephalopathies; Genetic diseases; Movement disorders; Mutation
Contributor Information
Liu Taotao
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Liu Xiaoli
Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai 201400, China
Wu Jingying
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Ni Ruilong
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Zhang Mengyuan
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Ji Duxin
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Zhang Mei
Department of Neurology, the First Affiliated Hospital of Anhui University of Science and Technology, Huainan 232001, China
Cao Li
Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
