Bulbar Onset Amyotrophic Lateral Sclerosis: A Case Report.

Amyotrophic lateral sclerosis is a rare, progressive, incurable neurodegenerative disorder that affects motor neurons leading to progressive muscle weakness, disability, and eventually death. A 45-year-old male, initially presented with hoarseness, flickering of tongue, and intermittent aspirations. In course of three years, patient developed motor aphasia, frequent aspirations and an inability to hold his neck. Patient was diagnosed with a bulbar onset type of amyotrophic lateral sclerosis on the basis of neurodegenerative features with normal radiographic imaging. For the prevention of recurrent aspiration pneumonia, he was managed with a percutaneous endoscopic gastrostomy tube. As he started developing respiratory failure tracheostomy was performed and kept on a continuous bi-level positive airway pressure ventilator, in the meantime, two courses of injection Edaravone were given. Early evaluation, diagnosis and management of the condition is a cornerstone for better prognosis of disease and survival. Keywords: amyotrophic lateral sclerosis; aspiration pneumonia; case reports; edaravone.

Intracranial Calcification and Seizure with Down Syndrome: A Case Report.

Down syndrome is a genetic disorder caused by an extra copy of chromosome number 21. New onset of seizure in adults with Down syndrome is rare. The exact pathogenesis of intracranial calcification and seizure in Down syndrome is unknown, however, a possible association between hypocalcemia and vitamin D deficiency in Down syndrome was reported. An 18-year-old girl with nasal bridge, mongoloid slants, clinodactyly and saddle gap of toes, and prominent Downs phenotypes was present with a low level of parathyroid hormone, calcium, and vitamin D. Due to a higher prevalence of intracranial calcification in people with Down syndrome, there is an increased possibility of hypocalcemia and vitamin D deficiency. Hence, serum levels of calcium and vitamin D should always be checked before starting treatment with anti-epileptic drugs. Keywords: basal ganglia; Down syndrome; seizure; trisomy 21.

D-penicillamine Induced Myasthenia Gravis in Wilson's Disease: A Case Report.

Myasthenia gravis is a neuromuscular junction disorder characterised by fluctuating muscle weakness, improved by using anti-cholinesterase drugs. In addition to the autoimmune aetiology, various factors such as infections, surgery, and drugs are known to precipitate the condition. We report a case of a 15-year-old boy with D-penicillamine-induced myasthenia gravis who presented with facial diplegia, dysphagia, and drooling of saliva, 6 years after the initiation of treatment for Wilson's disease. Therefore, clinicians should be more vigilant while prescribing patients with chelating drugs like D-penicillamine with regular monitoring of the new symptoms and keeping a very low threshold for the suspicion of myasthenia gravis. Keywords: d-penicillamine; myasthenia gravis; pyridostigmine; Wilson's disease.

Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver.

Dioxin-like molecules have been associated with endocrine disruption and liver disease. To better understand aryl hydrocarbon receptor (AHR) biology, metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor. Male wild type (WT) and Ahr -/- mice (Taconic) were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126) (61 nmol/kg by gavage) or vehicle for two weeks. PCB126 increased expression of canonical AHR targets (Cyp1a1 and Cyp1a2) in WT but not Ahr -/-. Knockouts had increased adiposity with decreased glucose tolerance; smaller livers with increased steatosis and perilipin-2; and paradoxically decreased blood lipids. PCB126 was associated with increased hepatic triglycerides in Ahr -/-. The liver proteome was impacted more so by Ahr -/- genotype than ligand-activation, but top gene ontology (GO) processes were similar. The PCB126-associated liver proteome was Ahr-dependent. Ahr principally regulated liver metabolism (e.g., lipids, xenobiotics, organic acids) and bioenergetics, but it also impacted liver endocrine response (e.g., the insulin receptor) and function, including the production of steroids, hepatokines, and pheromone binding proteins. These effects could have been indirectly mediated by interacting transcription factors or microRNAs. The biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.

Molecular characterization of distal 4q duplication in two patients using oligonucleotide array-based comparative genomic hybridization (oaCGH) analysis.

Pure/direct duplications on the long arm of chromosome 4 represent an infrequent chromosomal finding. Description of clinical findings in 30 patients has resulted in defining the 4q-associated phenotype. However, such duplications have not been molecularly or genomically characterized yet, limiting genotype-phenotype correlation. We report on the first two patients with a duplication involving the distal third of 4q that are characterized molecularly and genomically. Clinical features in our patients typical of 4q duplication syndrome included mild intellectual disability, cranial malformation, minor facial dysmorphism, and digital anomaly. Duplication of the segment 4q33-4q34, appears to be the critical region resulting in the phenotype associated with 4q duplication syndrome. The genes GLRA3, GMP6A that are invovled in neurogenesis and HAND2 in craniofacial development, within the duplicated region of 4q, may play a key role in the clinical phenotype. As more reporting on molecular characterization of 4q duplication becomes available, the role of these underlying genes may become clearer.