Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are probably 2.5 million patients with Paget's disease in the U.S.; 125,000 of these have severe disease meriting specific treatment. While the diagnosis can often be made by inspection, or by measurement of the temperature of involved limbs, it is often missed. Nonspecific findings include pain, headaches, deafness, heart failure, neurologic deficits and renal stones. A specific diagnosis can usually be established by radiologic examination of the skeleton and measurement of the serum alkaline phosphatase level. Bone scans are often helpful. In moderate-to-severe symptomatic disease, calcitonin limits the unregulated chaotic bone resorption and exerts highly specific and effective suppressive activity.
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PMID:Paget's disease: New treatment for an old disease. 13 63

Paget's disease usually is found in patients past the age of 40. Early presenting symptoms include headache, deafness, tinnitus, and pain due to radicular compression. The diagnosis is confirmed by radiographic features and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Bony overgrowth results in pressure on nearby soft tissues such as the brain, spinal cord, and certain peripheral nerves. The abnormally soft quality of the calvarial bone permits distortion by the weight of the brain. Dorsal inclination of the plane of the foramen magnum and the projection of the odontoid process into the posterior fossa lead to stretching of the brain stem over the odontoid process and the ventral margin of the foramen. Obstructive hydrocephalus may result. Sarcoma of the crainial vault may develop in cases of Paget's disease. Once cervicomedullary or spinal compression has occurred, surgical decompression may be necessary. Three drugs--calcitonin, disodium etidronate, and mithramycin--have been used with some benefit in the treatment of Paget's disease.
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PMID:Paget's disease and the nervous system. 21 14

Two distinct and characteristic cases of osteopetrosis are presented. The first concerns a fourth month old baby with the malignant form of the disease, initiated since the newborn period. He was admitted because of abnormal ocular movements and probably deafness. At the physical examination he showed bilateral optic atrophy, abnormal ocular movements, hepatosplenomegaly and petechia. The diagnosis was confirmed by clinical means and radiological studies of virtually all of his skeleton. Several fractures were found. Laboratory tests showed marked anemia, trombocytopenia "tear cells", evidence of medullary erythropoiesis and myelofibrosis. An increased alkaline phosphatase was detected in serum and in granulocytes. The second case corresponds to a 26 year-old female with the benign form of the disease. She had multiple pathological fractures specially of her lower limbs, that produced severe impotence in her gait. In this case, the diagnosis is suspected on clinical basis and confirmed with the characteristic radiological findings. Some of the more distinct features of the disease are discussed, specially those concerning the genetic mode of inheritance and consanguinity, the etiopathogenic, pathophysiology, clinical, laboratory, prognosis and treatment, with particular reference to the radiological and hematologic problems related with this metabolic disorder.
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PMID:[Osteopetrosis (report of 2 cases)]. 91 41

Waardenburg's syndrome (WS) is an autosomal dominant combination of deafness and pigmentary disturbances, probably caused by defective function of the embryonic neural crest. We have mapped one gene for WS to the distal part of chromosome 2. On the basis of their homologous chromosomal location, their close linkage to an alkaline phosphatase gene, and their related phenotype, we suggested that WS and the mouse mutant Splotch might be homologous. Splotch is caused by mutation in the mouse Pax-3 gene. This gene is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development; each contains a highly conserved transcription control sequence, the paired box. Here we show that some families with WS have mutations in the human homologue of Pax-3. Mutations in a related gene, Pax-6, which, like Pax-3, has both a paired box and a paired-type homeobox sequence, cause the Small-eye mutation in mice and aniridia in man. Thus mutations in the Pax genes are important causes of human developmental defects.
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PMID:Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. 153 45

Osteogenesis imperfecta (OGI) is a rare genetic disease which, as a result of a disorder in the formation of the organic stroma of the bone due to a defect in osteogenic function, induces brittle bones, whereby only weak forces bring about multiple, repeated pathological fractures. This disease is thought to entail various problems with regards to carrying out pediatric dentistry due to the ease with which bones may be fractured. We report here the findings obtained as a result of the careful examination of a 1-year-3-month-old girl encountered in our practice and who was diagnosed as having osteogenesis imperfecta. 1) Out of the three major symptoms for osteogenesis imperfecta, this case showed signs of fragile bones and blue scleras, but did not reveal signs of deafness. 2) There was retardation in system growth and development. 3) Aside from a high level of alkaline phosphatase, there were no notable abnormalities revealed in the biochemical blood tests. 4) Dentinogenesis imperfecta was observed throughout the erupted teeth. 5) There was a definite improvement in cooperation with each visit to the clinic.
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PMID:[Case report of osteogenesis imperfecta]. 215 62

Familial expansile osteolysis (FEO) is a unique bone dysplasia, which has, over five generations, affected 42 members of a Northern Ireland family. The disease follows a classic autosomal dominant pattern of inheritance. The condition is distinct enough in its clinical features and natural history to be recognized as a new and unique disease. There are both general and focal skeletal changes, the latter having a predominantly peripheral distribution and an onset from the second decade. Progressive osteoclastic resorption accompanied by medullary expansion leads to severe and painful disabling deformities with a tendency to pathologic fracture. Most affected members of the family have an associated early-onset deafness and loss of dentition as a result of unique middle ear and dental abnormalities. The serum alkaline phosphatase and urinary hydroxyproline are elevated to a variable degree, whereas other biochemical indices are normal. The response of the disease to a therapeutic trial using parenteral dichloro-methylene-diphosphonate (dichloro-MDP) produced an initial rapid biochemical response, which was not sustained.
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PMID:Familial expansile osteolysis. 253 18

In 56 patients with senile deafness, the degree of bone atrophy was quantitatively assessed by microdensitometry (MD). Biochemical examinations were also made. The following results were obtained: 1. Abnormal bone metabolism is suspected in many patients with senile deafness. 2. Serum calcium level is significantly lower and BUN significantly higher in patients with senile deafness than in normal subjects. 3. A significant positive correlation is noted between hearing levels and serum alkaline phosphatase levels in patients with senile deafness. After treatment of 12 patients suspected of having abnormal bone metabolism (as judged by MD) with an active vitamin D preparation (1 alpha-[OH]D3) at 1 microgram/day for 6 to 10 months, hearing improvement was noted for six ears (four patients). However, long-term observation is necessary to be able to assess the efficacy of active vitamin D on senile deafness, which is a result of chronic aggravation of hearing impairment.
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PMID:Senile deafness and metabolic bone disease. 320 26

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.
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PMID:Familial expansile osteolysis. A new dysplasia. 334 99

A prospective study of 47 patients with otosclerosis was undertaken to investigate the possible etiologic role of vitamin D undernutrition. The population comprised 27 women and 20 men, with a mean age of 46.4 years (range 21 to 79). The disease was bilateral in 43 patients, and cochlear involvement was present in 84.4%. The mean duration of symptoms was 17.1 years. Vitamin D status was evaluated by measuring the plasma 25-hydroxy vitamin D3 (25-OHD), which is the main storage metabolite. Abnormally low 25-OHD levels were found in 10 patients (21.7%) and borderline low levels in another two. Raised serum alkaline phosphatase levels were present in 32.6%, calcium in 6.5%, and inorganic phosphate in 4.3%. Calcium and vitamin D replacement therapy resulted in significant hearing improvement in 3 of 16 patients; these data support a causal correlation. Vitamin D deficiency is probably a factor in the etiology of some cases of otosclerosis and is important, since the deafness resulting from cochlear involvement may be reversible.
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PMID:Vitamin D deficiency and otosclerosis. 392 24

Tiludronate, a potent bisphosphonate, has been extensively evaluated in the treatment of Paget's disease of bone. Its ability to normalize bone turnover without impairing mineralization suggests that tiludronate represents an important therapeutic advance in the treatment of this progressive and disabling disease. Recent attention has focused on the development of appropriate short- and long-term treatment goals: namely the control of clinical symptoms, such as bone pain, and the reduction of bone turnover to within normal range, to lessen the risk of developing later complications, such as deafness, deformity and walking difficulties. This reduction of bone turnover is the primary aim of treatment. The clinical development of tiludronate has involved large-scale international multicenter trials. To allow the comparison of results obtained in a variety of clinical settings, great emphasis was placed on the use of consistent methodology across the program. This applied to patient selection, trial design, the evaluation of clinically meaningful effects of treatment and statistical analysis of results. Strict adherence to these principles has allowed us to compare the results of treatment with tiludronate in 85 centers in six countries across Europe. This paper illustrates the importance of clinical trial design in the evaluation of tiludronate and etidronate in the treatment of Paget's disease of bone, with a brief summary of results obtained from a recent comparative, prospective, double-blind, multicenter clinical trial. Effective suppression of bone turnover was assessed by monitoring the reduction in serum alkaline phosphatase and the ratio of urinary hydroxyproline/creatinine. Reduction in bone pain was assessed using Huskisson's visual analog scale. The results clearly show that tiludronate 400 mg/day for 3 months is more effective and as equally well tolerated as etidronate 400 mg/day.
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PMID:The methodology of clinical trials of oral tiludronate in Paget's disease of bone. 857 26


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