Late-Onset Leukodystrophy Mimicking Hereditary Spastic Paraplegia without Diffuse Leukodystrophy on Neuroimaging

Abstract

Tongxia Zhang,1,2 Chuanzhu Yan,1,3 Yiming Liu,1 Lili Cao,1 Kunqian Ji,1 Duoling Li,1 Lingyi Chi,2,4,5 Yuying Zhao1 1Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, People’s Republic of China; 4Brain Science Research Institute, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 5Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Lingyi ChiDepartment of Neurosurgery, Qilu Hospital, Shandong University, No. 107 Wenhua West Road, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel [phone]Email [email protected] ZhaoDepartment of Neurology, Qilu Hospital, Shandong University, No. 107 Wenhua West Road, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Leukodystrophies are frequently regarded as childhood disorders, but they can occur at any age, and the clinical and imaging patterns of the adult-onset form are usually different from the better-known childhood variants. Several reports have shown that various late-onset leukodystrophies, such as X-linked adrenoleukodystrophy and Krabbe disease, may present as spastic paraplegia with the absence of the characteristic white matter lesions on neuroimaging; this can be easily misdiagnosed as hereditary spastic paraplegia. The objective of this study was to investigate the frequency of late-onset leukodystrophies in patients with spastic paraplegia.Patients and Methods: We performed genetic analysis using a custom-designed gene panel for leukodystrophies in 112 hereditary spastic paraplegia-like patients.Results: We identified pathogenic mutations in 13 out of 112 patients, including five patients with adrenomyeloneuropathy, three with Krabbe disease, three with Alexander disease, and two with cerebrotendinous xanthomatosis. In terms of clinical manifestations, in addition to spastic paraplegia, three adrenomyeloneuropathy probands also had adrenocortical insufficiency, two Alexander disease probands developed urinary retention, one CTX proband developed cataracts and chronic diarrhea and the other presented with chronic diarrhea and mild tendon xanthomatosis. None of the patients had evidence of diffuse leukodystrophy on neuroimaging.Conclusion: Patients with late-onset spastic paraplegia should be screened for underlying leukodystrophies, irrespective of the presence of additional complicating symptoms and neuroimaging abnormalities.Keywords: targeted next-generation sequencing, pathogenic mutations, genetic causes, leukodystrophy frequency, magnetic resonance imaging

Keywords

• targeted next generation sequencing
• pathogenic mutations
• genetic causes
• leukodystrophy frequency，magnetic resonance imaging