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Progeria (Greek, "old age") refers specifically to Hutchinson-Gilford Progeria syndrome. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ...
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Hutchinson-Gilford Progeria syndrome is an extremely rare condition in which physical aspects of aging are greatly accelerated, and few affected children live past age 13. About 1 in 8 million babies are born with this condition. It is a genetic condition, but occurs sporadically and is usually not inherited in families. In biology, senescence is the combination of processes of deterioration which follow the period of development of an organism. ...
Scientists are particularly interested in progeria because it reveals clues about the normal process of aging.[1][2][3]
Symptoms
The earliest symptoms include failure to thrive (FTT) and a localized scleroderma-like skin condition. As the child ages past infancy, additional conditions become apparent. Limited growth, alopecia, and a distinctive appearance with small face and jaw and pinched nose all are characteristic of progeria. The people diagnosed with this disease usually have small, fragile bodies like those of elderly people. Failure to thrive is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in infancy. ...
Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen in the skin or other organs. ...
Alopecia is a set of disorders ranging from male and female pattern alopecia (alopecia androgenetica), to alopecia areata, which involves the loss of some of the hair from the head, alopecia totalis, which involves the loss of all head hair, to the most extreme form, alopecia universalis, which involves the...
Later the condition causes wrinkled skin, atherosclerosis and cardiovascular problems. The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ...
Cause Hutchinson-Gilford Progeria Syndrome (HGPS) is a childhood disorder caused by mutations in one of the major architectural proteins of the cell nucleus.
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. Because the "accelerated aging" diseases display different aspects of aging, but never every aspect, they are often called "segmental progerias". Werner syndrome is a very rare, autosomal recessive disorder whose most recognizable characteristic is premature aging. ...
It has been suggested that this article or section be merged with Cockayne syndrome. ...
Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the bodys normal ability to remove damage caused by ultraviolet (UV) light is deficient. ...
DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. ...
Diagnosis In HGPS patients, the cell nucleus has dramatically aberrant morphology (bottom, right) rather than the uniform shape typically found in healthy individuals (top, right) Diagnosis is suspected according to signs and symptoms, such as skin changes, abnormal growth, and loss of hair. It can be confirmed through a genetic test.[4]
Treatment No treatments have been proven effective. Most treatment focuses on reducing complications such as cardiovascular disease, such as heart bypass surgery or low-dose aspirin.[5] Children may also benefit from a high-calorie diet. A coronary artery bypass graft (CABG) or heart bypass is a surgical procedure performed in patients with coronary artery disease (see atherosclerosis) for the relief of angina and possible improved heart muscle function. ...
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Growth hormone treatment has been attempted.[6] Growth hormone (GH) is a protein hormone secreted by the pituitary gland which stimulates growth and cell reproduction. ...
A type of anti-cancer drug, the farnesyltransferase inhibitors (FTIs), have been proposed, but their use has been mostly limited to animal models.[7] A phase II clinical trial using the FTI Lonafarnib began in May 2007.[8] The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. ...
Prognosis There is no known cure. Few people with progeria exceed 13 years of age.[9] At least 90% of patients die from complications of atherosclerosis, such as heart attacks or strokes.[10]
Mental development is not affected. Individuals with the condition rarely live more than 16 years; the longest recorded life-span was 29 years.[citation needed] The development of symptoms is comparable to aging at a rate six to eight times faster than normal, although certain age-related conditions do not occur. Specifically, victims show no neurodegeneration or cancer predisposition. They also do not develop "wear and tear" conditions commonly associated with aging, like cataracts and osteoarthritis.[11] Neurodegeneration is progressive loss of structure or function of neurons, including death of neurons. ...
Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...
Cataract is also used to mean a waterfall or where the flow of a river changes dramatically. ...
Osteoarthritis (OA, also known as degenerative arthritis, degenerative joint disease), is a condition in which low-grade inflammation results in pain in the joints, caused by abnormal wearing of the cartilage that covers and acts as a cushion inside joints and destruction or decrease of synovial fluid that lubricates those...
Epidemiology One study from the Netherlands has shown an incidence of 1 in 4 million births.[12] Currently, there are 48 cases in the world.
Approximately 100 cases have been formally identified in medical history.[13][9]
Two families have been identified as having more than one child with the disease. The first was a family in India that has five children with progeria, two of which are now deceased. The eldest daughter with progeria is 19 years old, and their eldest son with progeria is 17, both having survived longer than typical among people with progeria. Their other living child with progeria is 7. The family was a subject of a 2005 Bodyshock documentary entitled The 80 Year Old Children. BodyShock is a scientific documentary series about the conditions or lives of extraordinary people. ...
In 2006, the Vandersweets, a family in Belgium, who already had one child diagnosed with progeria, were informed that their second child also had the disease.[14]
Research areas Several discoveries have been made that have led to greater understanding and perhaps eventual treatment.[15]
A 2003 report in Nature [16] said progeria may be a de novo dominant trait. It develops during cell division in a newly conceived child or in the gametes of one of the parents. It is caused by mutations in a LMNA (Lamin A protein) gene on chromosome 1. One of the authors, Leslie Gordon, was a physician who didn't know anything about progeria, until her own son, Sam, was diagnosed at 21 months. Gordon and her husband, pediatrician Scott Berns, founded the Progeria Research Foundation.[17] In medicine and genetics, a de novo mutation is a mutation which neither parent possessed or transmitted. ...
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A gamete (from Ancient Greek γαμετης; translated gamete = wife, gametes = husband) is a cell that fuses with another gamete during fertilization (conception) in organisms that reproduce sexually. ...
For linguistic mutation, see Apophony. ...
Lamin A is a protein that is found in the nucleus of the Eukaryotic organisms. ...
A representation of the 3D structure of myoglobin showing coloured alpha helices. ...
For other uses, see Gene (disambiguation). ...
Chromosome 1 is, by convention, the designation for the largest human chromosome. ...
Lamin A Nuclear lamina is a protein scaffold around the edge of the nucleus that helps organize nuclear processes such as RNA and DNA synthesis. The nuclear lamina is a dense, ~ 30 to 100 nanometers thick, fibrillar network composed of intermediate filaments made of lamin that lines the inner surface of the nuclear envelope in animal cells. ...
Scaffold may refer to: scaffolding as used in construction A gallows The Scaffold, UK musical group Scaffold - GNOME Development Environment Scaffold (Protein ECM) This is a disambiguation page — a navigational aid which lists pages that might otherwise share the same title. ...
HeLa cells stained for DNA with the Blue Hoechst dye. ...
For other uses, see RNA (disambiguation). ...
The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ...
Prelamin A contains a CAAX box at the C-terminus of the protein (where C is a cysteine and A is any aliphatic amino acids). This ensures that the cysteine is farnesylated, and this allows Prelamin A to bind membranes, specifically the nuclear membrane. After Prelamin A has been localized to the cell nuclear membrane the C-terminal amino acids, including the farnesylated cysteine, are cleaved off by a specific protease. The resulting protein is now Lamin A, is no longer membrane-bound and carries out functions inside the nucleus. The C-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free carboxyl group (COOH). ...
Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ...
In chemistry, non-aromatic and non-cyclic (acyclic) organic compounds are called aliphatic. ...
It has been suggested that this article or section be merged with Proteinogenic amino acid. ...
Prenylation or isoprenylation is the addition of hydrophobic molecules to a protein to facilitate its attachment to the cell membrane. ...
In HGPS the recognition site that the enzyme requires for the cleavage of Prelamin A to Lamin A is mutated. Lamin A cannot be produced and Prelamin A builds up on the nuclear membrane, causing a characteristic nuclear blebbing.[18] This results in the premature aging symptoms of progeria, although the mechanism connecting the misshapen nucleus to the symptoms is not known.
A study which compared HGPS patient cells with the skin cells from LMNA young and elderly human subjects found similar defects in the HGPS and elderly cells, including down-regulation of certain nuclear proteins, increased DNA damage and demethylation of histone leading to reduced heterochromatin.[19] Nematodes over their lifespan show progressive lamin changes comparable to HGPS in all cells but neurons and gametes.[20] These studies suggest that lamin A defects contribute to normal aging. Downregulation is the process by which a cell decreases the number of receptors to a given hormone or neurotransmitter to reduce its sensitivity to this molecule. ...
The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ...
Schematic representation of the assembly of the core histones into the nucleosome. ...
For differently-colored eyes, see Heterochromia. ...
Classes Adenophorea Subclass Enoplia Subclass Chromadoria Secernentea Subclass Rhabditia Subclass Spiruria Subclass Diplogasteria Subclass Tylenchia The nematodes or roundworms (Phylum nematoda from Greek (nema): thread + -ode like) are one of the most common phyla of animals, with over 80,000 different described species (over 15,000 are parasitic). ...
This article is about cells in the nervous system. ...
A gamete (from Ancient Greek γαμετης; translated gamete = wife, gametes = husband) is a cell that fuses with another gamete during fertilization (conception) in organisms that reproduce sexually. ...
In biology, senescence is the combination of processes of deterioration which follow the period of development of an organism. ...
Mouse model of progeria A mouse model of progeria exists, though in the mouse the LMNA prelamin A is not mutated, but instead ZMPSTE24, the specific protease that is required to remove the C-terminus of Prelamin A is missing. Both cases result in the build up of farnesylated Prelamin A on the nuclear membrane and in the characteristic nuclear LMNA blebbing. Fong et al use a farnesyl transferase inhibitor (FTI) in this mouse model to inhibit protein farnesylation of Prelamin A. Treated mice had greater grip strength, lower likelihood of rib fracture and may live longer than untreated mice.[21] A break or fracture in one or more of the bones making up the human rib cage. ...
This method does not directly 'cure' the underlying cause of progeria. This method prevents Prelamin A going to the nucleus in the first place so no Prelamin A can build up on the nuclear membrane, but equally there is no production of normal Lamin A in the nucleus. Luckily Lamin A does not appear to be essential, indeed mouse models in which the genes for Prelamin A and C are knocked out show no symptoms. This also shows that it is the build up of Prelamin A in the wrong place, rather than the loss of the normal function of Lamin A that causes the disease.
History Progeria was first described in 1886 by Jonathan Hutchinson[22] and also described independently in 1897 by Hastings Gilford.[23] The condition was later named Hutchinson-Gilford Progeria syndrome (HGPS). Year 1886 (MDCCCLXXXVI) was a common year starting on Friday (link will display the full calendar) of the Gregorian calendar (or a common year starting on Wednesday of the 12-day slower Julian calendar). ...
Sir Jonathan Hutchinson (1828-1913), English surgeon, ophthalmologist, dermatologist, venereologist and pathologist, was born on July 23rd, 1828 at Selby, Yorkshire, England, his parents belonging to the Religious Society of Friends (Quakers). ...
1897 (MDCCCXCVII) was a common year starting on Friday (see link for calendar). ...
See also Gerontology is the study of the elderly, and of the aging process itself. ...
A degenerative disease is a disease in which the function or structure of the affected tissues or organs will progressively deteriorate over time, whether due to normal bodily wear or lifestyle choices such as exercise or eating habits. ...
Farnsyltransferase - enzyme believed to play an important role in development of progeria and various forms of cancers. ...
A genetic disorder is a condition caused by abnormalities in genes or chromosomes. ...
Normal nuclear lamina (a and b) and mutant nuclear lamina (c and d) from a patient with HGPS, visualized by immunofluorescence - note the irregular and bumpy shape of the laminopathic nuclei[1] Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear...
This article is about the 1982 film. ...
Otherland is a four-volume science fiction epic by Tad Williams. ...
Robert Paul Tad Williams (born March 14, 1957) is the author of several fantasy and science fiction novels, including Tailchasers Song, the Memory, Sorrow, and Thorn series, the Otherland series, and The War of the Flowers. ...
References - ^ McClintock D, Ratner D, Lokuge M, et al (2007). "The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin". PLoS ONE 2 (12): e1269. doi:10.1371/journal.pone.0001269. PMID 18060063.
- ^ Hutchinson–Gilford Progeria Syndrome, Aging, and the nuclear Lamina, Bruce Korf, New England Journal of Medicine, 358:552-555 (February 7, 2008)
- ^ Phenotype and Course of Hutchinson–Gilford Progeria Syndrome, Melissa A. Merideth, Leslie B. Gordon, Sarah Clauss, et al., New England Journal of Medicine, 358:592-604 (February 7, 2008)
- ^ genome.gov. Retrieved on 2008-03-17.
- ^ Progeria: Treatment - MayoClinic.com. Retrieved on 2008-03-17.
- ^ Sadeghi-Nejad A, Demmer L (2007). "Growth hormone therapy in progeria". J. Pediatr. Endocrinol. Metab. 20 (5): 633–7. PMID 17642424.
- ^ Meta M, Yang SH, Bergo MO, Fong LG, Young SG (2006). "Protein farnesyltransferase inhibitors and progeria". Trends Mol Med 12 (10): 480–7. doi:10.1016/j.molmed.2006.08.006. PMID 16942914.
- ^ Phase II trial of Lonafarnib (a farnesyltransferase inhibitor) for progeria.
- ^ a b Steve Sternberg (April 16, 2003). Gene found for rapid aging disease in children. USA Today. Retrieved on 2006-12-13.
- ^ Progeria - MayoClinic.com. Retrieved on 2008-03-17.
- ^ genome.gov. Retrieved on 2008-03-17.
- ^ Hennekam RC (2006). "Hutchinson-Gilford progeria syndrome: review of the phenotype". Am. J. Med. Genet. A 140 (23): 2603–24. doi:10.1002/ajmg.a.31346. PMID 16838330.
- ^ Progeria - MayoClinic.com. Retrieved on 2008-02-06.
- ^ http://www.progeria.be/index_EN.php
- ^ Capell BC, Collins FS, Nabel EG (2007). "Mechanisms of cardiovascular disease in accelerated aging syndromes". Circ. Res. 101 (1): 13–26. doi:10.1161/CIRCRESAHA.107.153692. PMID 17615378.
- ^ M. Eriksson et al. (2003). "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome". Nature 423: 293–298.
- ^ Family Crisis Becomes Scientific Quest, Science, 300(5621), 9 May 2003
- ^ "Ageing nucleus gets out of shape" (March 2, 2006). Nature 440: 32–34. PMID 16511477.
- ^ Scaffidi P, Misteli T (May 19, 2006). "Lamin A-dependent nuclear defects in human aging". Science 312 (5776): 1059-–63. PMID 16645051.
- ^ Haithcock E, Dayani Y, Neufeld E, et al (2005). "Age-related changes of nuclear architecture in Caenorhabditis elegans". Proc. Natl. Acad. Sci. U.S.A. 102 (46): 16690–5. doi:10.1073/pnas.0506955102. PMID 16269543.
- ^ Loren G. Fong (March 17, 2006). "A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria". Science 311 (5767): 1621-–3. PMID 16484451.
- ^ Hutchinson, J. Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet I: 923 only, 1886.
- ^ Gilford, H. Ateleiosis and progeria: continuous youth and premature old age. Brit. Med. J. 2: 914-918, 1904.
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2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini (or common era), in accordance to the Gregorian calendar. ...
is the 76th day of the year (77th in leap years) in the Gregorian calendar. ...
A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...
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Among the hundreds of endocrine diseases (or endocrinological diseases) are: Adrenal disorders: Adrenal insufficiency Addisons disease Congenital adrenal hyperplasia (adrenogenital syndrome) Mineralocorticoid deficiency Conns syndrome Cushings syndrome Pheochromocytoma Adrenocortical carcinoma Glucose homeostasis disorders: Diabetes mellitus Hypoglycemia Idiopathic hypoglycemia Insulinoma Metabolic bone disease: Osteoporosis Osteitis deformans (Pagets...
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| Latin = hypophysis, glandula pituitaria | GraySubject = 275 | GrayPage = 1275 | Image = Gray1180. ...
Hyperpituitarism is the result of an overactive pituitary gland producing too much of the bodies natural growth hormones. ...
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Sheehan syndrome, also known as postpartum hypopituitarism or postpartum pituitary necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by necrosis due to blood loss and hypovolemic shock during and after childbirth. ...
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Pseudo-Cushings syndrome is a medical condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushings syndrome. ...
Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. ...
Lipoid congenital adrenal hyperplasia refers to an uncommon form of CAH resulting from defects in the earliest stages of adrenal cortisol synthesis: the transport of cholesterol into the mitochondria of the cells of the adrenal cortex and the conversion to pregnenolone. ...
3β-Hydroxysteroid dehydrogenase II deficient congenital adrenal hyperplasia (3βHSD CAH) is an uncommon form of CAH resulting from a defective gene for one of the key enzymes in cortisol synthesis by the adrenal glands. ...
11β-Hydroxylase deficient congenital adrenal hyperplasia (11β-OH CAH) is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene for the enzyme which mediates the final step of cortisol synthesis in the adrenal. ...
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene for the enzyme CYP17A1, which mediates several key transformations in the synthesis of both cortisol and sex steroids. ...
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, in all its forms, accounts for about 95% of diagnosed cases of congenital adrenal hyperplasia, and CAH in most contexts refers to 21-hydroxylase deficiency. ...
Conns syndrome is overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands. ...
Bartter syndrome is a rare genetic disease characterized by low potassium levels (hypokalemia), decreased acidity of blood (alkalosis), and normal to low blood pressure. ...
In medicine, adrenal insufficiency (or hypocortisolism) is the inability of the adrenal gland to produce adequate amounts of cortisol in response to stress. ...
Addisons disease(also known as chronic adrenal insufficiency, hypocortisolism or hypocorticism) is a rare endocrine disorder in which the adrenal gland produces insufficient amounts of steroid hormones (glucocorticoids and often mineralocorticoids). ...
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The gonad is the organ that makes gametes. ...
Polycystic ovary syndrome (PCOS, also known clinically as Stein-Leventhal syndrome), is an endocrine disorder that affects approximately one in ten women. ...
Premature Ovarian Failure (POF) is the cessation of menstrual periods and ovulation in women under the age of 40. ...
It has been suggested that this article or section be merged with Guevedoche. ...
17-beta-hydroxysteroid dehydrogenase deficiency is a rare disorder of sexual development which can produce impaired virilization (traditionally termed male pseudohermaphroditism) of genetically male infants and children and excessive virilization of female adults. ...
Hypogonadism is a medical term for a defect of the reproductive system which results in lack of function of the gonads (ovaries or testes). ...
Puberty is described as delayed when a boy or girl has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. ...
Precocious puberty means early puberty. ...
Androgen insensitivity syndrome (AIS, or Androgen resistance syndrome) is a set of disorders of sexual differentiation that results from mutations of the gene encoding the androgen receptor. ...
In medicine, autoimmune polyendocrine syndromes are a heterogenous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected. ...
Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. ...
Anna Haining Bates with her parents Greek gigas, gigantus (giant) is a condition characterized by excessive height growth and bigness. ...
People who are shorter have short stature. ...
Laron syndrome is a disorder characterized by an insensitivity to growth hormone, caused by a variant of the growth hormone receptor. ...
Psychogenic dwarfism, Psychosocial dwarfism or Stress dwarfism is a growth disorder that is observed between the ages of 2 and 15, caused by extreme emotional deprivation or stress. ...
Multiple endocrine neoplasia (MEN) (or multiple endocrine adenomas, or multiple endocrine adenomatosis -- MEA) consists of three syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. ...
Multiple endocrine neoplasia type 1 is part of a group of disorders that affect the endocrine system. ...
Multiple endocrine neoplasia type 2 is part of a group of disorders that affect the endocrine system. ...
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