Search

Purpose: To report the first case of ocular syphilis in an Iranian patient and discuss its diagnostic challenges. Case Report: A man in his mid-70s presented with progressive bilateral visual and auditory decline. He had previously lived in a Southeast Asian country for 10 years. Prior steroid therapies entailed no inflammation subsidence. His visual acuity at presentation was light perception OU. Funduscopic findings included severe vitritis, severe optic atrophy, diffuse retinal vascular occlusion, and diffuse retinal atrophy OU. Angiography demonstrated diffuse areas of retinal and choriocapillaris atrophy with no active choroiditis. Scaly cutaneous lesions were noted on his palms and soles -- atypical findings of secondary syphilis. Serum analysis revealed an underlying syphilis infection. The cerebrospinal fluid sample was reactive to anti-syphilis antibodies, securing a neurosyphilis diagnosis. Two weeks of antibiotic therapy resulted in cutaneous lesions resolution and relative visual improvement despite extensive baseline retinal atrophic damage. Conclusion: Ocular syphilis can mimic numerous ocular inflammatory scenarios. In cases of ocular inflammation that is unresponsive to steroids, reconsidering alternative diagnoses, especially infections with the highest clinical relevance, is necessary. We stress the importance of acquiring patients' sexual history, regardless of cultural barriers and the rarity of the entity in some regions. [ABSTRACT FROM AUTHOR]

Objective(s): Charcot-Marie Tooth disease (CMT) is one of the main inherited causes of motor and sensory neuropathies with variable expressivity and age-of onset. Although more than 70 genes have been identified for CMT, more studies are needed to discover other genes involved in CMT. Introduction of whole exome sequencing (WES) to capture all the exons may help to find these genes. Materials and Methods: Here, we tried to find the genetic cause of the neuropathy in two Iranian brothers using WES. Blood sample was collected from probands and their family members to extract the genomic DNA. The extracted DNA from one of the affected case was subjected for WES. The variant calls were filtered to reveal the pathogenic variant. Presence of the candidate mutation was confirmed using Sanger sequencing. The pathogenic potential of the variant was examined using in silico software. Using ClustalW multiple alignment, the presence of variant in conserved domain of protein was investigated. The parent and another affected boy were also checked for presence of the variant using PCR-sequencing. Results: The obtained data presented a novel TTC del mutation in CDS 738 of dystrophin related protein 2 (DRP2) gene, which was validated by sequencing. The variant was located in a conserved domain of DRP2 protein and predicted as pathogenic. Two affected boys were hemizygous for the mutation and received the mutation from mother. Conclusion: Here, we provided the evidence for the contribution of DRP2 in CMT. Also, the symptoms shed light on molecular aspect of this genetically heterogeneous disease. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Family Case Report of Niemman Pick C with New Mutation and Different Presentations" by Bita Shalbafan, is presented.

Alexander disease is a rare genetic disorder that predominantly affects infants and children and is associated with cerebral white matter disease. Intracytoplasmicastrocytic inclusions known as Rosenthal fibers are the hallmark of Alexander disease.Sporadic mutations in the GFAP gene are the cause of most cases of Alexander disease. Four subtypes of Alexander disease — neonatal, infantile, juvenile, and adult — are traditionally recognized but a revised classification of Alexander disease proposes two subtypes - types I and II - based upon statistical analyses: type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, sudden deterioration, and typical neuroimaging features Type II onset may occur across the lifespan, and is characterized by autonomic dysfunction, eye movement abnormalities, bulbar symptoms, and atypical neuroimaging features Typical MRI features of Alexander disease are:Extensive cerebral white matter changes with frontal predominance, Periventricular rim of high T1 signal and low T2 signal, Basal ganglia and thalamic abnormalities, Brainstem abnormalities, Contrast enhancement of selected gray and white matter structures Less common MRI features of Alexander disease include: Multifocal brainstem lesions resembling multiple tumors, Medullary and cervical spinal cord signal abnormalities or atrophy and Ventricular garlands The diagnosis of Alexander disease can be established based upon clinical and radiographic (MRI) features. The diagnosis is usually confirmed by demonstrating a GFAP gene mutation. Although genetic testing is not necessarily required for the diagnosis, genetic confirmation should always be attempted due to the heterogeneity of the disease and its presentation. The differential diagnosis of Alexander disease involves consideration of other disorders that present with macrocephaly and/or cerebral white matter changes. Treatment of Alexander disease remains supportive. Canavan disease or aspartoacylase deficiency is an autosomal recessive spongiform leukodystrophy that is prevalent in the Ashkenazi Jewish population. The disease typically begins in infancy and is marked by relentless progression. Aspartoacylase deficiency is caused by mutations in the ASPA gene that encodes the enzyme aspartoacylase. The resulting deficiency of aspartoacylase leads to accumulation of N-acetylaspartic acid (NAA) in brain and to oligodendrocyte dysfunction, spongiform changes, and absence of myelin. However, the precise mechanisms causing to spongiform degeneration are uncertain. Aspartoacylase deficiency typically presents at about age three months with lethargy and listlessness, weak cry and suck, poor head control, and hypotonia with a paucity of extremity movement. Macrocephaly becomes prominent by three to six months. Thereafter hypotonia progresses to spasticity and tonic extensor spasms. By age six months, neurologic abnormalities are invariant. Little subsequent development is noted. Blindness from optic atrophy occurs between 6 and 18 months. Seizures are noted in about 50 percent of patients. Pseudobulbar signs and decerebrate posturing dominate the end stage. The presence of variant forms of aspartoacylase deficiency is controversial. Brain imaging by CT and MRI reveals diffuse and symmetrical white matter involvement. The gross pathologic findings are dominated by spongy degeneration of deep cortex, subcortical white matter, and cerebellum. The spongiform changes reflect vacuolated astrocytes in deeper cortical layers and in adjacent subcortical white matter. In symptomatic infants with compatible clinical features (eg, hypotonia, poor head control, macrocephaly) and neuroimaging findings, the diagnosis of aspartoacylase deficiency is supported by elevated levels of urine N-acetylaspartic acid (NAA) and deficient aspartoacylase activity in cultured skin fibroblasts. Genetic testing may be obtained for purposes of genetic counseling. The differential diagnosis of aspartoacylase deficiency includes other progressive white matter diseases of infancy, particularly Krabbe disease, metachromatic leukodystrophy, early-onset adrenoleukodystrophy, Alexander disease, and demyelinating disorders. No effective treatment is available for aspartoacylase deficiency. Management is supportive and aimed at maintaining nutrition and hydration, protecting the airway, preventing seizures, minimizing contractures, and treating infections. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD) is a neurodegenerative disorder, which is the most common cause of dementia in the elderly. Accumulation of β-amyloid plaques outside neurons is the most important pathological hallmark of AD, which is produced by cleavage of amyloid precursor protein by the Alzheimer's β-secretase (BACE1). Since BACE1 is a key enzyme in the formation of β-amyloid peptides, the purpose of this study was to assess the association between polymorphisms of G/C (rs638405) BACE1 gene with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran. Methods: Genotypes were determined by the PCR--Restriction Fragment Length Polymorphism (PCR--RFLP) technique in two groups including 89 sporadic AD patients and 73 healthy subjects. Results: The findings of the BACE1 G/C (rs638405) polymorphism revealed that there was no significant difference between AD patients and controls in men group; however, there was a weak difference in the frequency of CC genotype between patients and controls in women group (χ²=3.333, df=1, p=0.068). Conclusion: The results of this study suggest that the G/C (rs638405) polymorphism of BACE1 gene might not be related with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran. However, our results do not support a genetic risk factor of this polymorphism for developing AD in male group of this study. [ABSTRACT FROM AUTHOR]