Search

Intellectual disability is a broad diagnosis encompassing a wide variety of overlapping phenotypes and severities. Genetic etiologies are found in approximately two-thirds of cases with underlying mutations ranging from large cytogenetic aberrations to point mutations and even epigenetic alterations. Diagnostic is challenging, be cause these conditions are genetically heterogenous with many different genetic alterations, which may manifest in clinically indistinguishable phenotypes. The diagnostic success often depends on diagnostic workflow of the patient. During the last few years enormous technical progress has been achieved in the area of molecular cytogenetics and molecular genetics, changing the recommendations of evaluation of children with intellectual disability. The stepwise approach of diagnostic evaluation increases the diagnostic yield and makes the use of expensive tools more rational. An optimal diagnostic evaluation starts with family history and genealogy, personal history and clinical evaluation, followed by differential diagnosis. When a specific genetic disorder is suspected, the confirmatory tests must be performed. However, according to the literature, in 65-85% of patients with ID no specific genetic/metabolic disorder is suspected after the first step of evaluation or the suspected diagnosis cannot be confirmed. In that case it is always important to look for additional clinical findings, and firstly the neuroimaging is recommended. If still no specific genetic disorder is suspected, molecular karyotyping is recommended, followed by X-linked genetic testing. Finally, screening for in born errors of metabolism in children with ID is indicated. However, even if all currently available diagnostic methods were applied, there would remain patients with intellectual disability of undetermined cause, and not always the appropriate tests for the suspected genetic disorders are available. In all these cases, where possible, it is important to store patient's cell line or DNA. Systematic follow-up of the patient should be carried out routinely. Further technical advances are necessary to enable investigation of other genetic mechanisms, including somatic mutation, epigenetic dysregulation and polygenic disruption, each of which is likely to account for a significant proportion of cases. [ABSTRACT FROM AUTHOR]

Leigh syndrome or subacute necrotizing encephalomyelopathy is one of the most common mitochondrial diseases in childhood. It is a progressive neurodegenerative disease with focal symmetric brain lesions mainly in the basal ganglia, thalamus, and brainstem which appear as hyperintense lesions on T2-weighted MRI. Presenting symptoms are mainly those of central or peripheral ner vous system, sometimes patients have dysmorphic features, cardiomyopathy signs, gastrointestinal, and kidney signs. The spectrum of neurological symptoms is wide from severe in fantile disease to subtle clinical manifestations. Psychomotor deay, seizures, ataxia, opticathrophy, dystonia, respiratory in sufficiency, polyneuropathy, and myopathy are the most frequent. Mutations in the genes encoding mitochondrial proteins are responsible for this syndrome, molecular genetic analyses confirm the diagnosisinal most 50% of Leigh syndrome patients. Clinical presentation, diagnostics and treatment issues are discussed in the article, also a case of Leigh syndrome is presented. The disease revealed itself during the first months of age with psychomotor delay, in fantile spasms, myopathy, swallow ing problems and respiratory failure. Hyperintense lesions on T2-weighted head MRI were found. Activity of pyruvate dehydrogenase complex activity was found to be de creased in myocytes and skin fibroblasts. Diagnosis of pyruvate dehydrogenase deficiency was further confirmed by moleculargenetic analysis of PDHA1 gene: a missense mutation (p.Arg378His) was found in the 11th exon of this gene. The disease course and applied treatment with ketogenic dieta as well as efficacy of this treatment is presented. [ABSTRACT FROM AUTHOR]

Background and Objective: Based on the results of many studies, the angiotensin-converting enzyme (ACE) and the α-actinin-3 (ACTN3) genes are considered strong candidate genes associated with human physical performance. On the other hand, the data regarding the association of the ACE I/D and ACTN3 R/X polymorphisms with human physical performance in different populations have been conflicting. The objective of our research was to evaluate the significance of these genetic variants on muscle performance phenotype in Lithuanian athletes., Material and Methods: The study involved 193 Lithuanian elite athletes and 250 controls from the general Lithuanian population. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Anthropometric measurements and muscle strength (grip strength and vertical jump) were measured., Results: It was determined that ACE I/I and I/D genotypes were more frequent in the athlete group compared with the general Lithuanian population. The results of grip strength and vertical jump were better in the athletes with the ACE I/I and ACTN3 X/X genotype compared with the athletes with ACE D/D and ACTN3 R/R, respectively., Conclusions: The ACE I and ACTN3 X alleles determine speed and power for Lithuanian athletes. In line with other researchers, it can be confirmed that the absence of a functional ACTN3 in fast-twitch muscle fibers is compensated. Lithuanian athletes who are carriers of the ACE I/I and I/D as well as ACTN3 X/X and R/X genotypes have the potential to achieve better results in power-requiring sports; therefore, the analyzed polymorphisms of these genes might be used as the criteria for the sport type selection.