Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report

Alexander disease is a heterogeneous group of diseases with various manifestations based on the age of disease onset. This rare leukodystrophy syndrome with mutations in the GFAP gene could present with developmental delay and seizure in the infantile form to ataxia and bulbar palsy in adulthood. However, psychiatric symptoms are not well-defined and are usually evaluated after disease diagnosis, not before disease investigations.

Our patient is a 52-year-old Iranian woman with a history of depression since 17 years ago, a suicidal attempt two years ago, and ingestion of a large amount of opium with the intention of suicide 2 months ago. She was presented with disorientation and probably a delirious state in the last interview. Eventually, in comprehensive investigations, white matter hyperintensity in MRI and leukodystrophy was diagnosed to determine the cause of these changes, we did a gene study, found whole exon deletion of the GFAP gene, and made a diagnosis of late-onset Alexander disease.

Neurological-onset manifestation of Alexander disease, specifically late-onset form, is the most common clinical picture of disease and was seen in about 90% of patients, but psychiatric symptoms are not well-known, and psychiatric-onset disease was not described yet. Various gene mutations were described in late-onset Alexander disease; however, the large whole exon deletion which was revealed in our patient is a novel mutation and significantly needs to be explored. Here authors describe a late-onset Alexander disease with psychiatric-onset symptoms and novel large exon deletion in the GFAP gene.

Alexander disease is a rare heterogeneous disorder that could have various symptoms of the central nervous system involvement.The whole-exons deletion of the GFAP gene in an adult patient with features of Alexander disease is the first Gene mutation that was revealed in this case.Psychiatric onset Alexander disease is the one differential diagnosis in the patients with atypical psychiatric symptoms combined with soft neurological signs.Neurologic consultation and appropriate imaging and laboratory procedures could help early diagnosis and potential treatment.

Patients with atypical psychiatric symptoms are usually visited more times in the year without any significant benefit. They receive numerous medications and encounter significant complications due to mentioned polypharmacy. However, genetic, metabolic, or neurological causes could be considered in some treatment-resistant cases. We described the rare genetic disorder(Late-Onset Alexander disease) in the Iranian woman with atypical and treatment-resistant depression with suicidal attempts. We proposed holistic assessment in the patients with psychiatric symptoms which have atypical course or response to treatment or are accompanied by neurological and cognitive symptoms.