Saturday, August 04, 2007 Too young to grow old By Lady Ochel Espinosa
THE term progeria narrowly refers to Hutchinson-Gilford Progeria syndrome, but the term is issued to describe any of the so-called "accelerated aging diseases". The word progeria is derived from the Greek for "old age".
Because the "accelerated aging" diseases display different aspects of aging, but never every aspect, they are often called "segmental progerias" by biogerontologists. Hutchinson-Gilford Progeria syndrome is an extremely rare genetic condition which causes physical changes that resemble greatly accelerated aging in sufferers. The disease affects between 1 in 4 million (estimated actual) and 1 in 8 million (reported) newborns. Currently, there are 51 known cases in the world. There is no known cure, but several discoveries have been made that have lead to greater understanding and perhaps eventual treatment. Most people with progeria die around 13 years of age.
Progeria is of interest to scientists because the disease may reveal clues about the process of aging. Unlike most other "accelerated aging diseases" (such as Werner's syndrome, Cockayne's syndrome or xeroderma pigmentosum), progeria is not caused by defective DNA repair.
The condition was first identified in 1886 by Jonathan Hutchinson and Hastings Gilford.
The condition was later named Hutchinson-Gilford Progeria syndrome (HGPS). Around 100 cases have been identified since then.
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. They also often suffer from symptoms typically seen in much older people: stiffness of joints, hip dislocations and severe, progressive cardiovascular disease. However, various other features associated with the normal aging process, such as cataracts and osteoarthritis, are not seen in children with progeria.
Some children with progeria have undergone coronary artery bypass surgery and/or angioplasty in attempts to ease the life-threatening cardiovascular complications caused by progressive atherosclerosis. However, there currently is no treatment or cure for the underlying condition. Death occurs on average at age 13, usually from heart attack or stroke.In 2003, NHGRI researchers, together with colleagues at the Progeria Research Foundation, the New York State Institute for Basic Research in Developmental Disabilities, and the University of Michigan, discovered that Hutchinson-Gilford progeria is caused by a tiny, point mutation in a single gene, known as lamin A (LMNA).
Parents and siblings of children with progeria are virtually never affected by the disease. In accordance with this clinical observation, the genetic mutation appears in nearly all instances to occur in the sperm prior to conception. It is remarkable that nearly all cases are found to arise from the substitution of just one base pair among the approximately 25,000 DNA base pairs that make up the LMNA gene.
The LMNA gene codes for two proteins, lamin A and lamin C, that are known to play a key role in stabilizing the inner membrane of the cell's nucleus. In laboratory tests involving cells taken from progeria patients, researchers have found that the mutation responsible for Hutchinson-Gilford progeria causes the LMNA gene to produce an abnormal form of the lamin A protein. That abnormal protein appears to destabilize the cell's nuclear membrane in a way that may be particularly harmful to tissues routinely subjected to intense physical force, such as the cardiovascular and musculoskeletal systems.
Interestingly, different mutations in the same LMNA gene have been shown to be responsible for at least a half-dozen other genetic disorders, including two rare forms of muscular dystrophy.
In addition to its implications for diagnosis and possible treatment of progeria, the discovery of the underlying genetics of this model of premature aging may help to shed new light on humans' normal aging process.
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.
