Open AccessSpastic paraplegia as the predominant phenotype in a cohort of Chinese patients with adrenoleukodystrophy
Author(s) -
Luo WenJiao,
Wei Qiao,
Dong HaiLin,
Yan YangTian,
Chen MeiJiao,
Li HongFu
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1065
Subject(s) - adrenoleukodystrophy , hereditary spastic paraplegia , medicine , proband , paraplegia , spastic , compound heterozygosity , spasticity , mutation , asymptomatic , phenotype , pathology , gastroenterology , genetics , biology , physical therapy , gene , peroxisome , receptor , cerebral palsy , psychiatry , spinal cord
Abstract Background X‐linked adrenoleukodystrophy (ALD) is one of the most common peroxisomal disorders characterized by abnormal accumulation of very long‐chain fatty acids (VLCFA) in plasma and tissues and caused by mutations within ABCD1 . Clinically, ALD present with various phenotypes, ranging from asymptomatic type to rapidly progressive childhood cerebral form. However, no remarkable abnormality in cerebral white matter usually makes it difficult to distinguish adult ALD from hereditary spastic paraplegia (HSP). Methods We analyzed the features of seven Chinese ALD patients who had a primary phenotype of spastic paraplegia. Sequencing was performed in the probands and their familial members. Detailed clinical, VLCFAs test, hormone test, magnetic resonance imaging, and electromyogram are presented. Results We reported seven ALD patients from a Chinese cohort of 142 HSP patients. Genetic investigations revealed five known ABCD1 mutations (c.346G>C, c.521A>G, c.829G>T, c.1415_1416delAG, and c.1849C>T) and two novel mutations (c.454C>G, c.1452_1482del). Further auxiliary testing revealed that they had higher VLCFA and/or adrenal insufficiency. Conclusions Our findings expand the mutation spectrum of ABCD1 and indicate that ALD represent a significant portion (4.9%, 7/142) of the spastic paraplegia entities. ALD should be considered in male patients with spastic paraplegia, even if there was no positive family history.