Initial frontal lobe involvement in adult cerebral X-linked adrenoleukodystrophy

Objective Adult cerebral X-linked adrenoleukodystrophy (ACALD) with initial frontal lobe involvement is a rare genetic disease that is easily misdiagnosed and underdiagnosed. We sought to improve the early identification of such diseases. Methods We present three cases of adult X-linked adrenoleukodystrophy (ALD) with initial frontal lobe involvement and identify an additional 13 cases from the database. The clinical and imaging characteristics of the overall sixteen cases were analyzed. Results The average age of onset was 37 years, with 15 male and 1 female patient. A total of 12 patients (75%) developed a decline in cerebral executive and cognitive functions. Brain trauma is the possible trigger for the onset of ALD in five patients (31%). An elevated level of very-long-chain fatty acids (VLCFA) was observed in all 15 patients on whom a plasma VLCFA was performed.10 patients with gene tests showed different mutation sites in the ABCD1 gene. Brain MRI of six patients (46%) were characterized by frontal lobe butterfly wings-like lesions with peripheral rim enhancement. Four patients underwent brain biopsies (patients 1, 3, 15, and 13), and five patients (31%) were initially misdiagnosed (patients 1, 2, 3, 11, and 15). Nine of the patients with follow-up records experienced poor prognoses, and five of them, unfortunately, died (56%). Conclusion ACALD patients with anterior patterns tend to be misdiagnosed. The early clinical manifestation is a decline in cerebral executive and cognitive function. Brain trauma may be a trigger for this pattern. Brain MRI findings are characterized by frontal lobe butterfly wing-like lesions with peripheral rim enhancement. The determination of the VLCFA levels and the genetic detection of the causative mutations are required to confirm the diagnosis.

Automated summary

In this study, we analyzed 16 cases of adult X-linked adrenoleukodystrophy (ALD) and found that frontal lobe involvement at the initial stage is a common clinical manifestation and is prone to misdiagnosis and underdiagnosis. The early clinical manifestation is a decline in cognitive and executive function. Brain trauma may be one of the triggers for this disease. MRI can reveal butterfly wing-like lesions in the frontal lobe. Confirmation of the diagnosis requires measurement of VLCFA levels and genetic testing.