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Progeria[edit]
Introduction[edit]
Progeria, also known as Hutchinson-Gilford progeria syndrome (HGPS), is a rare genetic condition that causes a child's body to age fast. A child in their teens with progeria often looks like someone who has lived 80 or 90 years. Most kids with progeria do not live past the age of 13. The disease affects both sexes and all races equally. It affects about 1 in every 4 million births worldwide. It is characterized by baldness, aged-looking skin, a pinched nose and a small face and jaw relative to head size. Children with progeria live to be only 13 years old on average. Death usually occurs as a result of heart attack or stroke.
Only 118 children have been identified as having progeria in the world today. This makes progeria one of the most rare childhood diseases that currently exists or is known. This is one of the reasons why research is slow in this area.Children with progeria often suffer from many of the same ailments that plague older adults, including stiffness of joints, hip dislocations and severe and progressive cardiovascular disease. Progeria is estimated to affect one in 8 million newborns worldwide, according to the NIH. Children with progeria initially appear normal during the first year of their lives, but symptoms soon begin to present in the form of slowed growth rate, shorter height measurements and lower weights than other children measured at their age.
One of the most remarkable aspects of progeria is that it does not affect the mind. Even though there are significant changes in the physical bodies of kids with this disease, the children who are diagnosed with progeria are very courageous, smart, and full of life.
As of 2014, the NIH is conducting research on people who live past the age of 100 to determine if they possess a unique gene that enables them to live longer. It is hoped that this gene can be utilized to prolong the lives of children with progeria.
Causes[edit]
HGPS is caused by a mutation in the gene called LMNA (pronounced, lamin - a). The LMNA gene produces the Lamin A protein, which is the structural scaffolding that holds the nucleus of a cell together. Researchers now believe that the defective Lamin A protein makes the nucleus unstable. That cellular instability appears to lead to the process of premature aging in Progeria. A single mistake in a certain gene causes it to make an abnormal protein. When cells use this protein, called progerin, they break down more easily. Progerin builds up in many cells of kids with progeria, causing them to grow old quickly.
Children with other types of progeroid syndromes which are not HGPS may have diseases that are passed down in families. However, HGPS is due to a sporadic autosomal dominant mutation – sporadic because it is a new change in that family, and dominant because only one copy of the gene needs to be changed in order to have the syndrome. For parents who have never had a child with progeria, the chances of having a child with progeria are 1 in 4 – 8 million. But for parents who have already had a child with progeria, the chances of it happening again to those parents is much higher – about 2-3%. This is due to a condition called mosaicism, where a parent has the genetic mutation for progeria in a small proportion of their cells, but does not have progeria.
Point mutation
In 2003, the cause of progeria was discovered to be a point mutation in position 1824 of the LMNA gene, in which cytosine is replaced with thymine.[16] This mutation creates a 5' cryptic splice site within exon 11, resulting in an abnormally short mature mRNA transcript. This mRNA strand, when translated, yields an abnormal variant of the prelamin A protein whose farnesyl group cannot be removed. Because its farnesyl group cannot be removed, this abnormal protein, referred to as progerin, is permanently affixed to the nuclear rim, and therefore does not become part of the nuclear lamina. Without lamin A, the nuclear lamina is unable to provide the nuclear envelope with adequate structural support, causing it to take on an abnormal shape.[17] Since the support that the nuclear lamina normally provides is necessary for the organizing of chromatin during mitosis, weakening of the nuclear lamina limits the ability of the cell to divide. The LMNA gene produces the lamin A protein which is the structural scaffolding that holds the nucleus of a cell together. The abnormal lamin A protein that causes Progeria is called progerin. Progerin makes the nucleus unstable. That cellular instability leads to the process of premature aging and disease in Progeria.
Progeria is not inherited, or passed down in families. The specific underlying cause of the accelerated aging associated with HGPS is not yet known. Many researchers suggest that the abnormal aging process is due to cumulative cellular damage resulting from ongoing chemical (metabolic) processes within bodily cells.
According to another theory, certain compounds called free radicals are produced during chemical reactions in the body. The increasing accumulation of free radicals within bodily tissues is thought to eventually cause damage to and impaired functioning of cells, ultimately resulting in aging. Certain enzymes (known as antioxidant enzymes) are believed to play a role in keeping the aging process “in check” by promoting the elimination of damaging free radicals. Enzymes are proteins produced by cells that accelerate the rate of chemical reactions in the body. Some researchers indicate that reduced activity of certain enzymes may play a role in causing accelerated aging in individuals with HGPS. In one study, skin cells (fibroblasts) obtained from individuals with progeria were compared with skin cells from individuals without the disease. In the fibroblasts of those with progeria, the activity levels of certain primary antioxidant enzymes (e.g., gluthathione peroxidase [GPx], catalase [CAT]) were significantly lower than the levels present in healthy fibroblasts. Further research is necessary to determine the implications of such findings.
Symptoms[edit]
Most kids with progeria look healthy when they're born, but they start to show signs of the disease during their first year. Babies with progeria do not grow or gain weight normally. They develop physical traits including:
- A bigger head
- Large eyes
- A small lower jaw
- A thin nose with a "beaked" tip
- Ears that stick out
- Veins you can see
- Slow and abnormal tooth growth
- A high-pitched voice
- Loss of body fat and muscle
- Hair loss, including eyelashes and eyebrows
Diagonosis[edit]
The diagnosis for progeria is difficult in early stages as newborns, children with progeria usually appear normal. However, within a year, their growth rate slows and they soon are much shorter and weigh much less than others their age. While possessing normal intelligence, affected children develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size.
A genetic test for Hutchinson-Gilford progeria syndrome, also called HGPS, is currently available. In the past, doctors had to base a diagnosis of progeria solely on physical symptoms, such as skin changes and a failure to gain weight, that were not fully apparent until a child's first or second year of life. This genetic test now enables doctors to diagnose a child at a younger age and initiate treatment early in the disease process.
This genetic test for Hutchinson-Gilford progeria syndrome also serves to reassure parents of affected children that their disorder stems from a sporadic genetic mutation and that therefore it is unlikely that any future offspring would have the condition.
Treatment[edit]
There's no cure for progeria, but regular monitoring for heart and blood vessel (cardiovascular) disease may help with managing the child's condition
Recent Improvements[edit]
Results of the first clinical drug trial for children with a rare rapid-aging disease, known as Progeria, has shown successfulness with a farnesyltransferase inhibitor (FTI), a drug first used to treat cancer.
The clinical trial results showed significant improvements in bone structure, weight gain, and most importantly, the cardiovascular system, according to new research published in Proceedings of the Natural Academy of Sciences. The two and a half year drug study consisted of 28 children from 16 different countries, accounting for 75 percent of Progeria cases worldwide. Twenty-six of the 28 children had the classic form of the disease. All 28 children traveled to Boston every four months to receive extensive medical testing through Children's Hospital's Clinical and Translational Study Unit.
The oral medication, the FTI lonafarnib, was given twice daily over the course of the study. The research team assessed the children's rate of weight gain, compared to their pre-study rate. They viewed this as the primary outcome because these kids suffer from critical failure to thrive, characterized by extremely slow weight gain over time. Researchers also inspected stiffness of the arteries (a predictor of heart attack and stroke), as well as bone rigidity and density (a predictor of osteoporosis). Every child participating in the study showed significant improvement in weight gain ability, bone structure, or flexibility of blood vessels.
Noteworthy Improvements:
Weight: One in three children demonstrated a greater than 50 percent increase in annual rate of weight gain, or switched from weight loss to weight gain, because of increased muscle and bone mass. Bone Structure: Bone rigidity improved to normal levels after FTI treatment. Cardiovascular: Arterial stiffness, associated with atherosclerosis, decreased by 35 percent. Vessel wall density also improved.
Case study[edit]
A six-year-old white girl was first seen at a hearing and speech clinic in rural Missouri. The childs mother brought her to the clinic seeking recommendations for special education facilities because
the child seemed “quite fragile” She was referred to a Medical Centre, Kansas City, Missouri,for evaluation, and diagnosis because of her obviously abnormal appearance.
Medical History
Pregnancy, labour and delivery were deemed normal by the mother except she received a series of injections in the sixth gestational month for a ‘poison ivy’ dermatitis. The newborn’s birth weight was 7lb2oz. The mother was aged 25 and the father was aged 26. She was the fourth of seven children. None of her siblings appear unusual. Early growth and development seemed normal according to the mother. Sat up at 11 months and potty trained by 2 years old. Seldom sweats and her skin seems much drier and darker than her siblings.
Physical Examination In appearance, the child seemed poorly nourished and poorly developed but claimed no distress during examination. Vital signs were normal, and her mental state was normal for a 6yr old. The skull appeared grossly abnormal with prominence of the frontal regions. The ears were prominent and low set. The lungs and heart and abdomen were normal on examination. The extremities seemed very thin, with long thing muscles. The digits were short, with considerable scarring. Neurologic examination was normal. The cholesterol levels appeared elevated above the normal childhood value. Many similar values in the adult are highly correlated with overt coronary sclerosis. The doctors claimed thet it was somewhat unique that she has reached the age of 6years without medical attention or intervention.
References[edit]
http://www.medicalnewstoday.com/articles/250725.php
http://www.mayoclinic.org/diseases-conditions/progeria/basics/treatment/con-20029424
http://www.progeriaresearch.org/about_progeria/
https://www.genome.gov/11007255/learning-about-progeria/
http://healthresearchfunding.org/7-interesting-facts-progeria/