Hypothesis: determining phenotypic specificity facilitates understanding of pathophysiology in rare genetic disorders

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

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Application of a Systematic Developmental Assessment to a Novel Population: Infants With Rare Genetic Disorders

Case Medical Research ◽

10.31525/ct1-nct03967743 ◽

2019 ◽

Author(s):

Keyword(s):

Genetic Disorders ◽

Developmental Assessment

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Faculty Opinions recommendation of PTC124 targets genetic disorders caused by nonsense mutations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1083014.542194 ◽

2007 ◽

Author(s):

Albert La Spada

Keyword(s):

Genetic Disorders ◽

Nonsense Mutations

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Statins in Aortic Disease

Current Pharmaceutical Design ◽

10.2174/1381612823666171115100829 ◽

2018 ◽

Vol 23 (46) ◽

pp. 7109-7120

Author(s):

Vasiliki Tsigkou ◽

Gerasimos Siasos ◽

Evanthia Bletsa ◽

Maria-Paraskevi Panoilia ◽

Angeliki Papastavrou ◽

...

Keyword(s):

Aortic Valve ◽

Genetic Disorders ◽

Aortic Disease ◽

Current Data ◽

Valve Regurgitation ◽

Aortic Diseases ◽

Cochrane Database ◽

Effect Of Treatment ◽

Pleiotropic Actions ◽

Optimal Type

Background: Numerous studies indicate that statins have multiple beneficial actions (known as ‘pleiotropic actions') on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, excessive arterial thrombosis, and stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardioprotective actions of statins in aortic disease. Objective: Our aim was to present current data concerning the value of treatment with statins in aortic diseases. Methods: A thorough search of PubMed and the Cochrane Database was conducted to identify the studies and novel articles related to the use of statins in aortic disease. Results: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data. Conclusion: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease.

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Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus

Current Pharmaceutical Design ◽

10.2174/1381612823666171109112307 ◽

2018 ◽

Vol 24 (1) ◽

pp. 62-77 ◽

Cited By ~ 13

Author(s):

Sayed Sartaj Sohrab ◽

Sherif Aly El-Kafrawy ◽

Zeenat Mirza ◽

Mohammad Amjad Kamal ◽

Esam Ibraheem Azhar

Keyword(s):

Enzymatic Degradation ◽

Polymeric Nanoparticles ◽

Genetic Disorders ◽

Inorganic Nanoparticles ◽

Innovative Technology ◽

Viral Diseases ◽

Viral Gene ◽

Efficient Delivery ◽

Disease Therapy ◽

Target Sites

Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.

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