Progeria is also known as the syndrome of Hutchinson-Gilford progeria or HGPS. Progeria syndrome is a severely occasional condition of gene where indicators similar to features of elderly are shown at a primary age. Progeria is among the many conditions of progeroid. The term progeria is coined from the Greek terminologies pro which means premature or before, and geras which means oldness. The condition is associated with a very low prevalence rate happening in an approximated one per every eight million living childbirth. Those progerian babies are characteristically able to survive to their premature twenties and mid-teens. Progeria is a disorder of a gene that takes place as a first hand mutation, and it is occasionally inherited since carriers mostly do not survive to replicate. Nonetheless, the phrase progeria is applicable exactly when referring to the entire diseases featured by pre-mature symptoms of aging, and it is usually applied like that when particularly referring to Hutchinson-Gilford progeria syndrome . Scientists are specifically concerned about progeria since the condition may disclose indications regarding the aging processes. Progeria was initially defined in 1886 by Jonathan Hutchinson. The definition was followed by another independent description in by Hastings Gilford in 1897. Thus, the disorder was called Hutchinson-Gilford syndrome . This research work aims to define progeria into detail and how to diagnose it. Further, the work looks into the symptoms of progeria as well as its treatment and finally concludes on the matter.
How to Diagnose Progeria
Diagnosis of progeria is alleged with regards to signs as well as syndromes, for example, changes in the skin, growth abnormality and hair loss. Further, a genetic test for mutations in LMNA is a surety of progeria.
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Symptoms of Progeria
Children diagnosed with progeria mostly develop their initial symptoms at the early months of their lifetime. The most first syndrome comprise of a letdown to grow or increase and a confined somewhat scleroderma illness of the skin. As the child develops above early period, more disorders become obvious mostly around the ages of 18 to 24 months. The characteristics include limited growth, loss of hair or alopecia on the whole body, and a unique appearance such as small face characterized with jaw that is shallowly recessed and pinched-like nose (Carvalho et al. 2016). The signs and symptoms of the developing condition appear to be more recognized as the child grows old.
After sometime, the disorder results into skin that is wrinkled, failure of the kidney, atherosclerosis, eyesight loss and problems associated with the cardiovascular. Scleroderma, or tightening and hardening of the skin around trunk as well as the body extremities are common. Individuals identified with this illness commonly have bodies that are small and fragile similar to that of an elderly person. Their faces are mostly wrinkled, and have larger head which is not proportional to their body, their face are narrow as well as beak nose. Besides, protruding scalp veins are identifiable and are made clearer by alopecia and conspicuous eyes. Loss of muscles and body fats, stiff joints, dislocation of hip as well as other symptoms which are mostly lacking in the population of non-elderly are caused by the degeneration of musculoskeletal. However, persons associated with the disorder mostly maintain their normal motor and mental development (Collins, 2016).
Treatment of Progeria
There are no treatments that have proven to be effective. Several treatments aim at lessening the complications, for instance, the cardiovascular conditions together with the bypass surgery of the coronary artery or administration of aspirin of low doses. Children can as well benefit from diets of high energy. However, treatment of hormonal development has been endeavored. Besides, the usage of morpholinos has been as well tried to lessen progerin production. Thus, it involved the usage of morpholino oligonucleotides which is an antisense particularly focused on the modified exon 11 to exon 12 junctions in the modified pre-mRNAs. Possible therapeutic places for the progerin farnessylation inhibition include a drug type for anticancer known as the farnesyltransferase (FTIs). Farnesyltransferase (FTIs) has been suggested but their usage is extremely limited to models of animals. In May 2007, a clinical endeavor at phase II by use of FTI lonafarnid started (Carvalho et al. 2016).
In cell studies, rapamycin, another drug of anti-canncer, caused progerin amputation from the membrane of the nuclear via autophagy. Research has confirmed that zoledronate and pravastatin are appropriate drugs. The drugs are effective in blocking the farnesyl group production. Nevertheless, it is essential to recall there is no able cure for progeria condition. Farnesyltransferase inhibitors (FTIs) refer to medications that hinder an enzyme processes required to create a relation between farnesyl groups and proteins of progerin. The relation creates a solid connection of the protein of progerin to the rim of the nuclear.
In progerin condition, the destruction of a cell can be treasured since that connection occurs and the nucleus is in an abnormal condition. Lonafarnib is a FTI, thus it can evade the linkage, so that progerin dissociates from the nucleus rim thus it has recognizable standard condition. The delivery of lonafarnib has not yet been confirmed by the United States Administration on Food and Drug (FDA). Thus the administration only recommended for particular clinical attempts. Until the implementation of the FTIs treatments in progeria children, there is a possibility of establishing its impacts that are of benefit to mice. Pravastatin, also known as selektine as well as pravachol is one among the family of statins (King and Heyer, 2013).
Zeledronate also referd to as Reclast and Zometa and which are bisphosphonate is used in the HGPS to prevent the formation of farnesyl group. Farnesyl group is required by progerin to provoke the condition. Some attempts in Animals have been shown using the FTIs as well as the combination of zeledronate and pravastatin to make observations whether they are able to reverse abnormal nuclei. The outcome, which was gathered by an assessment of electron microscopic which is blinded and a microscopy of immunofluorescence, revealed that deformities due to nucleus could be retreated in mice of transgenic trait articulating progerin. The process of reversion was as well disclosed in vivo. Vivo are cells that are cultured from items of human with progeria. This was as a result of pharmacs, which play a role in blocking protein prenylation, that is, the farnesyl polypeptide relocation to C-terminal cysteine. In addition, according to the authors of the trial add, skin biopsy can be of benefit to indicate if protein farnesylation inhibitors can exert effects on items with HGPS in clinical endeavors (King and Heyer, 2013).
As opposed to FTIs, zoledronate and pravastatin were certified by the United States FDA in 2006 as well as 2001 consecutively, however, they are never sold for progeria treatment. Pravastin is used to lessen levels of cholesterol whereas zoledronate is used in the prevention of hypercalcaemia. Also, Rapamycin otherwise called Sirolimus functions as macrolide. Current explorations on rapamycin concluded that is able to lessen the impacts of phenotype of fibroblastic Progeria. Other noticeable outcomes due to its usage include the nuclear blebbing abolishment, progerin degradation in the mutilated cells, as well as decrease in the formation of progerin which is insoluble. However, the entire results are not from clinical trials but, it is alleged that the treatment may be advantageous to the HGPS patients. A clinical trial in 2012 established that Lonafarnib, the drug for cancer can enhance gain in weight as well as other symptoms of progerin (Tsiligiri, 2015).
Conclusion
Many findings have been advanced that have led to higher appreciation as well as ultimate curing of the condition. According to Nature report, progeria has the ability of being a de novo prevailing characteristic. Progeria develops in a form of zygote that is newly conceived and either of the parents’ gametes during cell division. Progeria is caused as a result of LMNA mutations, the gene of lamin A protein that is located on chromosome 1 and, that progerin is the modified type of lamin A.
References
Carvalho, V. O., Celli, A., Bancke Laverde, B. L., Cunico, C., Santos Piedade, G., Lucas de Mello, M., & Beirao Junior, P. S. (2016). Progeria and the early aging in children: a case report. Dermatology online journal , 22 (2).
Collins, F. S. (2016). Seeking a Cure for One of the Rarest Diseases: Progeria. CIRCULATIONAHA, 134 (20), 116.
King, A. A., & Heyer, G. L. (2013). Moving from gene discovery to clinical trials in Hutchinson-Gilford progeria syndrome. Neurology , 81 (5), 408-409.
Tsiligiri, M., Fekos, C., Theodoridou, E., & Lavdaniti, M. (2015). An Overview of Hutchinson Gilford Progeria Syndrome (HGPS). British Journal of Medicine and Medical Research , 5 (12), 1527.
