The Reality of Old Age – Hutchinson-Gilford Progeria Syndrome

As kids we all want to grow up but for about 1 child in 4 million, it’s a painful reality. Hutchinson-Gilford progeria syndrome (HGPF) is a rare genetic disorder determined by symptoms of aging appearing in early childhood, and a child with this syndrome ages approximately 8 times faster than average. With only around 140 cases being reported since it was first described in 1886 and no known cure, it’s a horrible disease for the unfortunate few.

HGPF is most commonly diagnosed in the first 3 years of life and usually by the appearance of the skin, where skin is generally shiny and lacks elastic properties, similar to that of an elderly person. Other common early signs are hair loss, a failure to thrive and poor weight gain. The most life-threatening symptoms of the disorder, however, are cardiovascular problems that lead to heart attacks or strokes. Children with progeria often have atherosclerosis which develops in early childhood and is the underlying cause of cardiovascular problems. Other effects of the disorder include dental overcrowding and a high pitched voice.

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  Even though the disease is very rare, geneticists are aware of the exact mutation that causes the disorder. This is a point mutation, meaning one base pair in a sequence is altered. In Hutchinson – Gilford progeria, the altered base pair in on the first chromosome (with thymine being used instead of cytosine), in the position q22 in a gene known as LMNA. Other mutations around this point cause diseases such as muscular dystrophy.  In HGPS the affected gene encodes for a protein known as prelamin A which has farnesyl group attached to it, a protein modification that helps proteins attach to a membrane, in this case the nuclear lamina. Normally this farnesyl group is eventually removed allowing the protein to be released but in Hutchinson-Gilford progeria the farnesyl group remains attached. This leads to an abnormally shaped nuclear lamina rim which doesn’t provide the nuclear envelope with support and therefore limits the ability of the cell to divide.

At present there is no cure and most treatment plans work to relieve the symptoms and stop major problems, especially cardiovascular ones, from becoming any worse. Anticancer drugs known as farnesyltransferase inhibitors (FTI’s) are thought to have some effect on slowing down the progress of Hutchinson – Gilford progeria syndrome as they stop the farnesyl group from being added to the prelamin A. The drugs are still in trial phases but there have been some success with children showing improvement in bone and blood vessel structure. Even though children with HGPF are biologically older than those at a similar physical age, they are able to lead relatively normal lives as their disease appears to have no effect on them mentally. Children are often able to attend school and participate in extracurricular activities. Whilst the disease is rare, a research foundation has been set up by the family of Sam Berns, who was diagnosed in 1998. In 2003, the foundation were involved in the research that located the mutation in the gene that causes Hutchinson-Gilford progeria syndrome. Although Sam Berns passed away earlier in 2014, the foundation still continues to carry out research in the hope of one day finding a cure.

Bethany

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References:

Hamosh, A. (2014, April 6). Hutchinson-Gilford Progeria Syndrome. Retrieved July 2014, from Online Mendelian Inheritance in Man: http://omim.org/entry/176670

Genetics Home Reference (2007, July). Hutchinson-Gilford Progeria Syndrome. Retrieved July 2014, from Genetics Home Reference: ghr.nlm.nih/gov/condition/hutchinson-gilford-progeria-syndrome

Hennekam, R. (2006). Hutchinson-Gilford Progeria Syndrome: Review of the Phenotype. American Journal of Medical Genetics , 2603-2624.

Zhang, H., Chen, X., & Guo, Y. (2013). Hutchinson-Gilford progeria syndrome: Report of 2 cases and a novel LMNA mutation of HGPS in China. Journal of the American Academy of Dermatology , 175-176.

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