Giant axonal neuropathy: The first Iranian case with a variation in the gigaxonin gene and a glance to the other cases

Background: Giant axonal neuropathy (GAN) is a very rare fatal neurodegenerative disorder with clinical and allelic heterogeneity. The disease is caused by mutations in the GAN (gigaxonin) gene. Herein, we reported the clinical presentations and results of genetic analysis of the first Iranian GAN case. Methods: Phenotypic data were obtained by neurologic examination, brain magnetic resonance imaging (MRI), electromyography (EMG), electroencephalography (EEG), and sonography from the proband. Deoxyribonucleic acid (DNA) was isolated from peripheral blood leucocytes and whole exome sequencing (WES) was performed. The candidate variant was screened by Sanger sequencing in the proband and her family members. Results: The proband was a 7-year-old girl who was admitted with a chief complaint of ataxia, muscle weakness, delayed developmental milestones, and history of psychiatric disorders. She was very moody and had clumsy gait, decreased deep tendon reflexes (DTRs) of lower limbs, and kinky hair. The brain MRI revealed white matter abnormality. The EMG revealed that her disease was compatible with the chronic axonal type of sensorimotor polyneuropathy; however, her EEG was normal. Results of the WES revealed a homozygous variant; c.G778T:p.E260* in the GAN gene, indicating the GAN disorder. Conclusion: The present study affirmed GAN allelic heterogeneity and resulted in the expansion of the phenotypic spectrum of GAN pathogenic variants. Identification of more families with mutations in GAN gene helps to further understand the molecular basis of the disease and provides an opportunity for genetic counseling especially in the populations with a high degree of consanguineous marriage such as the Iranian population.

A-088 Case Report: Neuropsychological Assessment of Giant Axonal Neuropathy in Adulthood

Objective Giant axonal neuropathy (GAN) is a progressive condition marked by abnormally large/dysfunctional axons. Childhood neurological symptoms (e.g., ataxia, loss of sensation, strength, and reflexes in limbs, and visual and hearing problems) eventually lead to central nervous system impairment (e.g., seizures, paralysis, and cognitive decline). The scant literature on cognition in GAN is mixed, with findings from no impairment all the way to dementia. We present a case of an adult GAN patient with milder symptoms. Method A 55-year-old Hispanic male with 13 years of education was referred from outpatient neurology for neuropsychological evaluation in a county hospital setting. He was symptomatic in childhood, but was not diagnosed with GAN until 2018. A comprehensive neuropsychological evaluation was conducted. His presentation was notable for anxious and restricted affect, rapid speech, and intense gaze. He appeared immature and at times guarded about his symptoms and history. Results Cognitive test results were valid and indicated normal-range IQ and generally intact cognitive abilities with mixed performances (and mild deficits) in visual memory and executive functioning. The MMPI-2-RF was invalid due to elevations on multiple validity scales, possibly due to limited insight and/or impression management (L-r highest). Conclusions The results add to the limited literature on cognition in GAN by describing a milder case. Our patient demonstrated some mixed cognitive difficulties as well as idiosyncrasies in personality that could reflect immaturity and/or reduced insight. In addition to further exploring its cognitive effects, future research into GAN should include the evaluation of personality and insight/metacognition in patients with milder symptoms.