Hutchinson-Gilford Progeria Syndrome

Hutchinson-Gilford Progeria Syndrome, otherwise known as Progeria, is an extremely rare genetic disorder that manifests as aging at a very early age. This disorder has a low incidence and occurs in one per eight million live births. Ninety percent of children with Progeria have a gene mutation that on the gene that encodes lamin A.

This disorder is considered a genetic disorder because it is a result of a gene mutation. The gene responsible for Progeria is called LMNA. A point mutation in the DNA sequence causes this mutation. The LMNA gene normally makes a protein called lamin A, which is an important protein for most of the cells in our body. Lamin A is found in the cell nucleus and helps maintain the shape and function of the cell. In Progeria, the LMNA mutation causes the gene to produce an abnormal protein called progerin. In children with Progeria, many cells in the body make the progerin protein. As the children age, progerin builds up in these cells causing the disease to progress. Everyone's body makes progerin, although in much lower results than children with Progeria. The gene is not normally inherited but occurs as a result of a new gene mutation during the early division of cells in the child. The mutation is considered a sporadic, autosomal, dominant mutation. There is a family in India that has five children all of whom have Progeria and another family in Belgium that have 2 children with Progeria.

Progeria was described in 1886 by Jonathan Hutchinson and separately in 1887 by Hastings Gilford. Currently there are between 35 and 50 known cases of Progeria in the world. These occurrences have been reported in many countries including the US, England, Japan, China, Mexico and many more. In 2003, the gene for Progeria was discovered and this discovery is helping researches to find a cure as well as give insight into the adult aging process.

Progeria symptoms affect the body in the same way that aging does although the symptoms manifest much younger and at a much faster rate. Some of the symptoms include growth failure, loss of body fat, aged looking skin, hair loss, arthritis, cardiovascular disease and stroke. Children with Progeria, often die very young, ranging in age from eight to twenty one. There have been few cases where the child has lived into their adult years. While this gene mutation expresses in the body, it does not express in the brain so children with Progeria still have the mindset of any child their age.

Progeria is an extremely rare disorder only manifesting in one in eight million children. There are other forms of the disease including Werner's syndrome, the adult version of Progeria, which manifests in the late teen years. There have been approximately 100 cases in medical history and there are currently 35 to 50 diagnosed cases worldwide.

Two of the main indicators of Progeria are insulin resistant diabetes and skin changes similar to those in scoleroderma, the skins become tough and hardened. Since the discovery of the gene, doctors now have a test for Progeria. In the past, diagnosis was based on physical symptoms but this genetic test allows doctors to diagnose children at younger ages and initiate early treatment. This genetic test also serves to reassure parents that this gene mutation will not affect future offspring.

At this point in time, there is no treatment for Progeria. Doctors suggest that children with Progeria are put onto an aspirin regimen which will help promote heart health. Once the child exhibits symptoms such as hypertension, strokes or seizures, the child may be put onto treatments similar to those given to adults. Anti-seizure, anti-coagulants, and anti-hypertensive medications are often given to children with Progeria. It is also recommended that children with Progeria undergo MRI's to screen for neurological changes and stroke symptoms. It is also recommended that children with Progeria consume nutritional supplements such as Ensure or Boost since their body requires more calories. Children with Progeria often have decreased visual and auditory acuity.

There are three drugs currently being studied for use in children with Progeria. These drugs are Farnesyltransferase Inhibitor (FTI), a statin called Pravastatin, and bisphosphonate called Zoledronic Acid. All three of these drugs work in different places along a common pathway that is affected by Progeria. FTIs are a class of drugs that inhibit en enzyme that is required to attach the farnesyl group to proteins. Since progerin is a protein that needs to be farnesylated to fully function, the FTI prevents this attachment. Pravastatin is normally used to lower cholesterol and preventing cardiovascular disease. It is being used in children with Progeria to block the production of the farnesyl molecule that is needed to create Progeria. Children with Progeria can have low bone density and Zoledronic Acid may, over time, help with that problem. It also has an effect on blocking the production of the farnesyl molecule.

The rare genetic disorder, Progeria causes early aging in children and is a result of a sporadic, autosomal dominant gene mutation. Children with Progeria don't normally live beyond their teenage years and at this point there is no cure for Progeria. Scientists discovered the Progeria gene in 2003 and are currently performing clinical trials to try and find a cure.