Typical and atypical phenotype and neuroimaging of X-linked adrenoleukodystrophy in a Chinese cohort

Objective The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD. Methods Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed. Results The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular “butterfly wings” like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found. Conclusions We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.