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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.

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Background and Objective: Attention deficit hyperactivity disorder (ADHD) is a common behavioral problem in children. Identifying the associated risk factors of ADHD is very important for the prognosis and early diagnosis of the disease. Here, we evaluated the association between lead exposure and growth indexes in children with ADHD. Materials and Methods: This case-control study was conducted on 30 children with ADHD and 50 healthy subjects. The patient’s age was between 5-12 years. Demographic and clinical information of children were recorded. Blood lead levels were measured in all samples by atomic absorption spectrometry. Results: Children with ADHD had significantly higher mean BMI than the control group (16.54 ± 2.8 kg/m2 vs. 14.82 ± 1.68 kg/m2; p=0.001). The mean of blood lead in children with ADHD was significantly higher than the normal group (10.58 ± 8.06 μg/dl vs. 7.52 ± 2.26 μg/dl; p=0.01). Multiple logistic analysis revealed one unit increase in BMI was associated with a higher risk of ADHD by 1.5 times (P=0.005; OR = 1.50), while one unit increase in blood lead level increased the risk of ADHD by 1.15 times (P=0.03, OR=1.15). Conclusion: Higher BMI and blood lead concentration are risk factors for ADHD among Iranian children.

Background: Leigh syndrome (LS) is a rare and inherited disease which is associated with progressive neurological disorders. The molecular underlying mechanism in LS is defined with some defects in mitochondrial respiratory chain enzymes. Case presentation: Here, an 8-year-old girl is reported with bilateral horizontal gaze palsy, ataxia and drowsiness. She developed unsteady gait, drowsiness, progressive ataxia and intention tremor during her admission period. The laboratory tests were reported within normal values including biochemical, hematological, immunological, infectious and inflammatory markers and blood and cerebrospinal fluid (CSF) lactate. Brain magnetic resonance imaging (MRI) demonstrated dorsal midbrain, bilateral putamen nuclei and cerebellar dentate nucleus involvement. Ocular examination revealed retinal atrophy and pale disk in both sides. These symptoms were in favor of a neurodegenerative disorder. Magnetic resonance spectroscopy (MRS) revealed an elevated lactate peak in involved areas which suggested a mitochondrial disease. Finally, the molecular genetic test reported NDUFS4 gene mutation which confirmed the presence of Leigh syndrome. She responded significantly to mitochondrial treatment cocktail and clinical signs and symptoms improved gradually. NDFUS4 gene encodes a subunit of mitochondrial complex I (NADH: ubiquinone oxidoreductase) that removes electrons from NADH and transfers them to the electron acceptor ubiquinone. Conclusion: Our findings indicated that various symptoms and clinical features can be found in Leigh syndrome which could be probably due to different mutations in mitochondrial genes. Therefore, appropriate clinical and laboratory settings along with brain MRI, MRS and genetic test analysis would be necessary for the early diagnosis.