Hypophosphatasia is a rare genetic bone disorder characterized by osteoblast hyperactivity and bone remodeling with loss of, or incomplete, mineral deposition. It is comparable to osteomalacia and rickets, but maintains a unique set of characteristic identifiers (Mornet 2008; Brickley and Ives 2008). Also called, Rathbun’s Syndrome, hypophosphatasia can be autosomal dominant or autosomal recessive depending on the individual. Severe forms are usually transmitted as autosomal recessive with a recurrence risk of 25 percent, while milder forms can be transmitted as either autosomal dominant or autosomal recessive, with between 25-50 percent recurrence rates (Mornet 2008). Hypophosphatasia has an incidence rate of 1 in 100,000 live births (Brickley and Ives 2008; Wendling et al. 2001). In half of all cases, the condition is fatal.
Mutations within the liver/bone/kidney alkaline phosphatase gene (ALPL) that encodes for tissue non-specific alkaline phosphatase (TNAP) inhibits the mineralization of bone by causing a deficiency of TNAP (Mornet 2008). Regularly, TNAP is dephosphorylated and the inorganic phosphate that is knocked off is used for hydroxyapatite crystallization. If inorganic pyrophosphates (PPi), which are formed when ATP is hydrolyzed into AMP, are not dephosphorylated by TNAP, then hydroxyapatite deposition is inhibited (Mornet 2008).
There are six forms of hypophosphatasia recognized: perinatal lethal; infantile; childhood; adult; odontohypophosphatasia; and perinatal benign. In the first form in utero osteochondral spurs can form on the fore arms and legs (Mornet 2008). The fetus is unable to make it to term and is aborted within few days. The perinatal benign form often shows change in the formation of the spurs but de...
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...cht über die biologisch-anthropologische Literatur 70:249-60.
Brickley, Megan, and Rachel Ives.
2008 The bioarcheology of metabolic bone diseases. Academic Press p 259
Formicola, Vinczeno.
1995 X-linked hypophosphatemic rickets: a probable upper Paleolithic case.
American Journal of Physical Anthropology.98(4):403-9.
Hérasse, Muriel with Marc Spentchian, Agnes Taillandier, and Etienne Mornet.
2002 Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients. European Journal of Human Genetics. 10(10):666-8.
Mornet, Etienne
2008 Hypophosphatasia. Best Practice & Research Clinical Rheumatology
Wendling, Daniel with Laurence Jeannin-Louys, Patrick Kremer, Florence Fellmann, Éric Toussirot and Étienne Mornet
2001 Adult Hypophosphatasia. Current Aspects. Joint Bone Spine 68(2):120-124
Fibrodysplasia ossificans progressiva also known as FOP is a one of the rarest, most disabling genetic bone conditions known to medicine. FOP causes muscles, tendons, ligaments, and other connective tissues to turn in to bone. Movement becomes limited in the affected areas of the body. People with FOP typically have malformed toes at birth, meaning the big toe is typically shorter than normal and abnormally turned outward in a position called a valgus deviation. Symptoms of FOP start to show up in early childhood. Most people with FOP develop painful tumor-like swellings also known as fibrous nodules. The fibrous nodules are visible on the neck, shoulders, and back.
In order to study the gene mutation that is supposed to cause Paget’s Bone Disease researchers had to have viable candidates to host the gene mutation. They found the best candidate to host the gene mutation in mice so they implanted the gene mutation in embryos of mice offspring. The researchers hypothesized that p62P394L is sufficient to induce PDB, especially since the p62 gene is responsible for encoding 62 kDa protein which functions in signaling osteoclast precursors. Results were found by fixing the first through fifth lumbar vertebra of four, eight, and twelve month old homozygote, heterozygote and WT littermates in 10% buffered formalin for 24- 48 hours. The first through fourth vertebra were then completely decalcified while the fifth was not. Longitudinal sections of both decalcified and undecalcified vertebra were cut, mounted on glass slides and stained to analyze. The mice with p62P394L had histologically normal bones, indicating that p62 mutation is not enough to induce Paget’s disease of the bone in vivo, there are additional factors necessary. Knowing osteitis deformas is due to hyper responsive multinucleated osteoclasts, it seemed a sensible suggestion. However, there are many other variables that should be factored when considering possible causes for osteoclast hyperformation. If p62P349L is present, doesn’t necessarily mean a person will get PDB, though an environmental factor such as measles could easily open up transduction pathways that could eventually lead to pagetic bone lesions. We find this study to be a stepping stone for future researchers to use in order to actually identify what causes Paget’s bone disease. (Hiruma, Kurihara, Subler, Zhou, Boykin, Zhang, Ishizuka, Dempster, Roodman & Wi...
Achondroplasia (ACH) is the most common form of short-limb dwarfism occuring in 1 in 15,000 to 28,000 births and appears to be slightly more prevalent in females, but indiscriminent toward race (1-3). Evidence has been found in Egypt for cases of ACH dating back as far as 4500 B.C. (4). In simplest terms, ACH is a disease where the dwarfing of bones formed in the cartilage occurs (5). There are many features that accompany this disease including rhizomelic (proximal) shortening of the extremities, megalencephaly (enlarged brain), short stature, trident hand, and frontal bossing (prominent forehead) (1, 3, 4, 6-8). Expression of this gene at high levels is primarily found in cells of the nervous system and the cartilage rudiments and chondrocytes in the growth plates of developing bone (7, 9). Due to the fact that there are numerous types of skeletal dysplasia, some which appear similar to ACH at times, the only way for complete confirmation is to perform molecular techniques such as genetic testing (1, 4, 8).
The head is unable to grow normally, which can lead to a misshapen skull, widely spaced eyes, and a bulging forehead. At birth, the bones of the skull are not joined together; they close up as the child grows. In Jackson-Weiss syndrome, the skull bones join together too early. This is called "craniosynostosis." Foot abnormalities are the most consistent characteristic, as not all individuals with Jackson-Weiss syndrome have abnormal skull or facial features. The big toes are enlarged and bend away from the other toes. They have very different ways off forming in the feet including the big toes are short and wide, the big toes also bend away from other toes, and the bones of some toes may be fused together which they call “syndactyly” or abnormally
Most serious structure with regards to Osteogenesis Imperfecta , the greater part of these cases are endless in great conditions, which means the vast majority of the cases wind up in premature birth by the guardians or unnatural birth cycle by nature . In any case, a portion of the uncommon cases that do survive present breathing challenges much of the time deadly at or soon after birth, regularly because of respiratory
Conforming to Melmed, Polonsky, Larsen & Kronenberg (2011) the waste products of the blood can form crystals which can collect inside the kidneys and aggregate to form stones. Normally the stones are composed of phosphate, oxalate, uric acid, and magnesium ammonium phosphate, single or combined. The type of stone is determined by the pathogenic mechanisms. When the stones are find in the bladder, ureters, renal tubules and collecting system they tend to be symptomatic. When the urine is oversaturated with the stones constituents the stones are formed. During the passage through the renal tubules the crystals aggregate into stones. In order to allow more time for growth the crystals anchor themselves to the renal tubular epithelium in the renal papillae and Randall’s plaques. The concentration of excreted ions is influenced by the diet. The intake of fluids can reduce the stone formation and growth. A reduction in the sodium int...
Bones of the skeletal system serve as storage compartments for vital minerals like phosphorus and calcium. Excessive calcium in the blood is stored in bones. Calcium is released from the bones into the blood when there are deficient amounts of it in the blood.
Albert Einstein once said, “Blind belief in authority is the greatest enemy of truth.” As a society, we have been taught, trained some may say, to avoiding independent thought and be submissive to the information we are taught during the course of our life. The question is sometimes asked, do our role models encourage meaningful learning and reflection? In the essay, “Diagnosing and Treating the Ophelia Syndrome” Author, Thomas G. Plummer, a professor at the University of Minnesota and at Brigham Young University, emboldens both students and the public to strive for self reliant thought through some diversified methods. Plummer talks about the play Hamlet, more specifically the character Ophelia, as the fundamental example, as someone who was
Osteoporosis is a serious disease that leads to a faster than normal loss of the bone density, which puts the bone at a higher risk for fractures. In order to understand the causes of Osteoporosis, it is important to understand how bones are formed. Bone is a living tissue that is made mainly of collagen, calcium phosphate, and calcium carbonate. The mixture of collagen and calcium gives the bone strength and flexibility. The body deposits new bones and removes old ones; moreover, there are two types of bone cells that control the reproduction of bones. Cells called osteoclasts breakdown bone tissues thus, damaging the bone. Once the damaged bone is removed, cells called osteoblasts, use minerals including calcium and phosphate from the blood stream to make new healthy bone tissues. In order for osteoblasts and osteoclasts to work properly, hormones such us thyroid, estrogen, testosterone, and growth hormones are
Khan, Aneal. “Williams Syndrome.” Ed. Stuart Berger. Medscape. WebMD, 12 Mar. 2012. Web. 15 Feb. 2014. .
Osteoporosis is a disease in which the bones become so weak and brittle that even a cough can cause enough stress on the bone that it will cause the bone to facture. The most commonly broken bones are the hip, wrist, and the spine. Although it affects men and women of all races, post-menopausal Caucasian and Asian women are more commonly affected than those of other ethnicities and sexes. In fact, thirty percent of all post-menopausal women in the US and Europe will be diagnosed with Osteoporosis and at least 40 percent of those will suffer from a fracture in their lifetime.
Type IV of OI is much rarer, comprising only 5% of cases. The bones may appear normal at the time of the first...
The syndrome is caused because of Genetic mutation that replaces connective tissues (muscles) with bones when someone gets injured instead of getting cured. This results in a new skeletal structure. Unfortunately this syndrome does not have any cure and the patients are advised to always be careful and not to fall or have any kind of traumas. They can’t engage in any sports in order to prevent any injuries. Surgery for removal of extra bones is not an option because removal of bones will lead to ingrowth of more bones. From previous cases it is seen that most of the patients suffering from this condition do not live more than 40 years and they die of respiratory
Hydrocephalus is a genetic disorder commonly described as “water on the brain.” In actuality, this is a condition in which there is an excessive accumulation of cerebrospinal fluid (CSF), a clear watery fluid that surrounds the space between the brain and spinal cord, in the brain. Normally, the production together with the absorption process of CSF is specifically balanced to ensure that the brain tissue remains buoyant, that nutrients can be delivered and waste removed, and that there is a compensation for changes in intracranial blood volume. Hydrocephalus blocks this balanced flow as well as absorption, and on account of CSF being produced continuously, 16 oz each day to be exact, the blocking creates a surplus of CSF resulting in the said pressure against the brain tissue. The surplus accretion of CSF additionally motivates ventricular dilation in which the gaps between the brain, known as ventricles, abnormally widen.
Other metabolic bone diseases are osteoporosis, gout, OSTEOARTHRITIS, and PAGET'S DISEASE. Nutritional Disorders Nutritional deficiencies that result in bone damage include RICKETS in children and osteomalacia in adults, caused by a lack of vitamin D. In children, calcium and phosphate are poorly distributed on bones during development, resulting especially in deformity of the legs and arms. In adults, bones of the spine, pelvis, and legs become demineralized and the bones weaken.