Background Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder caused by mutations in the ABCD1 gene. The clinical manifestations of ALD vary widely with some patients presenting with adrenomyeloneuropathy (AMN) that resembles the phenotype of hereditary spastic paraplegia (HSP). The aim of this study is to investigate the frequency, spectrum, and clinical features of ABCD1 mutations in Taiwanese patients with HSP phenotype. Methods Mutational analysis of the ABCD1 gene was performed in 230 unrelated Taiwanese patients with clinically suspected HSP by targeted resequencing. Clinical, electrophysiological, and neuroimaging features of the patients carrying an ABCD1 pathogenic mutation were characterized. Results Ten different ABCD1 mutations were identified in eleven patients, including two novel mutations (p.Q177Pfs*17 and p.Y357*) and eight ever reported in ALD cases of other ethnicities. All patients were male and exhibited slowly progressive spastic paraparesis with onset ages ranging from 21 to 50 years. Most of them had additional non-motor symptoms, including autonomic dysfunction in nine patients, sensory deficits in seven, premature baldness in seven, skin hyperpigmentation in five, psychiatric symptoms in one and cerebellar ataxia in one. Seven of the ten patients who ever received nerve conduction studies showed axonal polyneuropathy. Magnetic resonance imaging (MRI) revealed diffuse spinal cord atrophy in seven patients, cerebral white matter hyperintensity in one patient, and cerebellar involvement in one patient. Conclusions ABCD1 mutations account for 4.8% (11/230) of the cases with HSP phenotype in Taiwan. This study highlights the importance to consider ABCD1 mutations in patients with clinically suspected HSP of unknown genetic causes.
