PROGERIA---RARE OLD AGE DISEASE

PROGERIA

17-YEAR OLD BOY DIED OF RARE OLD AGE DISEASE

Sam Berns, a high school student, who suffered from Progeria, a very rare premature aging disease, died.Progeria is a fatal genetic disease characterized by the appearance of accelerated aging, according to the Progeria Research Foundation. An estimated 200 to 250 children worldwide suffer from the disease at any given time, with an average life expectancy of 13 years.Berns was diagnosed with progeria at 22-months-old. His parents, who work as doctors, established the foundation in 1999, with an aunt to find a cause, treatment and cure for the disease.In an interview, Berns encouraged other children who are struggling to overcome their challenges, and said that he did not want anyone to feel bad for him."No matter what problems you are facing, there is always room for happiness," Berns said.

Progeriais an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. Progeria is one of several progeroid syndromes. The word progeria comes from the Greek words "pro" (πρό), meaning "before" or "premature", and "gēras" meaning "old age". The disorder has a very low incidence rate, occurring in an estimated 1 per 8 million live births.Those born with progeria typically live to their mid teens to early twenties.It is a genetic condition that occurs as a new mutation, and is rarely inherited, as patients usually do not live to reproduce. Although the term progeria applies strictly speaking to all diseases characterized by premature aging symptoms, and is often used as such, it is often applied specifically in reference to Hutchinson–Gilford progeria syndrome (HGPS).

Scientists are particularly interested in progeria because it might reveal clues about the normal process of aging Progeria was first described in 1886 by Jonathan Hutchinson.It was also described independently in 1897 by Hastings GilfordThe condition was later named Hutchinson–Gilford progeria syndrome.Children with progeria usually develop the first symptoms during their first few months of life. The earliest symptoms may include a failure to thrive and a localized scleroderma-like skin condition. As a child ages past infancy, additional conditions become apparent usually around 18–24 months. Limited growth, full-body alopecia, and a distinctive appearance (a small face with a shallow recessed jaw, and a pinched nose) are all characteristics of progeria. Signs and symptoms of this progressive disease tend to become more marked as the child ages. Later, the condition causes wrinkled skin, atherosclerosis, kidney failure, loss of eyesight, and cardiovascular problems. Scleroderma, a hardening and tightening of the skin on trunk and extremities of the body, is prevalent. People diagnosed with this disorder usually have small, fragile bodies, like those of elderly people. The face is usually wrinkled, with a larger head in relation to the body, a narrow face and a beak nose. Prominent scalp veins are noticeable (made more obvious by alopecia), as well as prominent eyes. Musculoskeletal degeneration causes loss of body fat and muscle, stiff joints, hip dislocations, and other symptoms generally absent in the non-elderly population. Individuals usually retain normal mental and motor development.In normal conditions, the LMNA gene codes for a structural protein called prelamin A. There is a farnesyl functional group attached to the carboxyl-terminus of its structure. The farnesyl group allows prelamin A to attach temporarily to the nuclear rim. Once the protein is attached, the farnesyl group is removed. Failure to remove this farnesyl group permanently affixes the protein to the nuclear rim. Without its farnesyl group, prelamin A is referred to as lamin A. Lamin A, along with lamin B and lamin C, makes up the nuclear lamina, which provides structural support to the nucleus.

Before the late 20th century, research on progeria yielded very little information about the syndrome. 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. This mutation causes transcription of the LMNA gene to stop too early, which results in the creation of an abnormally short 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 shapeSince 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 divideProgerin may also play a role in normal human aging, since its production is activated in senescent wildtype cells

Unlike "accelerated aging diseases" (such as Werner syndrome, Cockayne syndrome or xeroderma pigmentosum), progeria is not caused by defective DNA repair. Because these diseases cause changes in different aspects of aging, but never in every aspect, they are often called "segmental progerias.Diagnosis is suspected according to signs and symptoms, such as skin changes, abnormal growth, and loss of hair. A genetic test for LMNA mutations can confirm the diagnosis of progeria

Prof. John Kurakar