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

Hypophosphatasia is a heritable metabolic bone disease with characteristically reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and bone. ALP levels are normal in the intestine and placenta. About 300 patients have been reported so far in the literature. Three kindreds with 52 known subjects are described here, whereby 12 subjects could be examined osteologically. Four subjects were patients and had clinical signs of the disease: spontaneous fractures of the metatarsals or femora and low ALP serum levels ranging between 8 and 23 U/l (normal range 40-170 U/l). Four other members without fractures had reduced ALP levels; they might be carriers of the disease and develop symptoms later in life. The four remaining subjects had normal ALP levels and no signs of the disease. Serum levels of intact parathyroid hormone (iPTH) were found to be in the lower normal range and serum calcium levels in the upper normal range. There was a significant (P less than 0.05) negative correlation between iPTH and serum calcium levels (r = -0.78). Urinary calcium excretion was increased in 3 subjects with fractures. 25-OH-D3 levels were increased in 6 of 8 subjects without any treatment. The bone mineral density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine, representing mainly trabecular bone, and single-photon absorptiometry of the forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged between 0.38 and -1.95 SD; Z-scores of the forearm bone mass ranged between 0.53 and -2.47 SD with the lowest values in patients with fractures.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Reduced bone mineral density and low parathyroid hormone levels in patients with the adult form of hypophosphatasia. 139 24

Serum levels of alkaline phosphatase (AP) have been used in the clinical evaluation of numerous diseases, including malignancies, for half a century. The aberrant expression of AP genes in cancer cells has led to the suggestion that APs are oncofetal proteins and thus, could be involved in tumorigenesis. Tumors which express these AP isozymes can be broadly divided into two groups: (a) those with an enhanced production of an isozyme normally expressed in the tissue (eutopic expression) and (b) those showing expression of one or more isozymes not identified in the normal tissue (ectopic expression). Moreover, many tumors show simultaneous expression of two or more different AP isozymes. In the absence of known biological functions of the AP isozymes several different mechanisms underlying their expression in tumor cells could explain the findings. In an attempt to clarify the function of APs, this laboratory is engaged in the study of unique properties of the mammalian APs as possible clues to their function, i.e., (a) the phosphatidylinositol glycan attachment of APs to the cytoplasmic membrane, (b) the uncompetitive inhibition properties of APs and (c) the extracellular matrix binding domain of APs. This laboratory is also undertaking the task of targeting each of the mouse AP isozymes by homologous recombination to generate mouse models of hypophosphatasia to analyze in detail the in vivo consequences of AP isozyme deficiencies.
 ...
PMID:Alkaline phosphatase as a reporter of cancerous transformation. 139 34

Hypophosphatasia is a heritable form of rickets/osteomalacia with extremely variable clinical expression. Severe forms are inherited in an autosomal recessive fashion; the mode of transmission of mild forms is uncertain. The biochemical hallmark of hypophosphatasia is deficient activity of the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Previously, we demonstrated in one inbred infant that an identical missense mutation in both alleles of the gene encoding TNSALP caused lethal disease. We have now examined TNSALP cDNAs from four unrelated patients with the severe perinatal or infantile forms of hypophosphatasia. Each of the eight TNSALP alleles from these four individuals contains a different point mutation that causes an amino acid substitution. These base changes were not detected in at least 63 normal individuals and, thus, appear to be causes of hypophosphatasia in the four patients. (Two additional base substitutions, found in one allele from each of the four patients, are linked polymorphisms.) Twenty-three unrelated patients (of 50 screened), who reflect the entire clinical spectrum of hypophosphatasia, possess one of our of the above eight mutations. In two of these additional patients, mild forms of the disease are also inherited in an autosomal recessive fashion. Our findings indicate that hypophosphatasia can be caused by a number of different missense mutations and that the specific interactions of different TNSALP mutant alleles are probably important for determining clinical expression. Severe forms, perinatal and infantile disease, are largely the result of compound heterozygosity for different hypophosphatasia alleles. At least some cases of childhood and adult hypophosphatasia are inherited as autosomal recessive traits.
 ...
PMID:Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. 140 20

Hypophosphatasia is an inherited disorder characterized by defective mineralization of the skeletal and dental structures of the body and deficient liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. There has been a tremendous advance in our knowledge of this condition over the last decade due to the advent of highly specific DNA probes and novel microanalytic techniques. The purpose of this paper is threefold: to review the dental aspects of current literature about this rare condition; to present a case (and family study) that was diagnosed in a 5-yr-old boy from 0.14 microliters of gingival crevicular fluid, using a new ultrasensitive chemiluminescent assay for the enzyme alkaline phosphatase; and to provide strong evidence for an autosomal dominant mode of inheritance.
 ...
PMID:Hypophosphatasia: a family study involving a case diagnosed from gingival crevicular fluid. 143 39

Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. The clinical expression of the disease is highly variable, but in early life the severity tends to reflect the age of onset. Accordingly, the disease is often classified into perinatal, infantile, and childhood forms. Hypophosphatasia also occurs in adults. Some exhibit symptoms in adulthood for the first time, but others have a history of the disease in early life with an intervening symptom-free period. Defective mineralization of bones and teeth is the predominant clinical feature of all forms of the disease. Biochemically, the reduction in ALP activity is associated with alterations in the extracellular metabolism of various phosphorylated compounds, including inorganic pyrophosphate (PPi), phosphoethanolamine, and pyridoxal 5'-phosphate. Of these, PPi may have an especially important role in the development of the mineralization defect. Accordingly, the extracellular metabolism of PPi and its possible role in the regulation of mineralization will be discussed.
 ...
PMID:Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects. 164 80

Prenatal diagnosis was attempted in a pregnant Japanese woman whose son had died of infantile hypophosphatasia, using chorionic villi sampled at 10 weeks of gestation. Southern blot analysis of restriction fragment length polymorphism was used as a guide, with cDNA for the human liver-type alkaline phosphatase as a probe, and BclI as a restriction enzyme. The fetus was found to be a heterozygote; the pregnancy was allowed to continue; and the baby born was phenotypically normal.
 ...
PMID:Prenatal diagnosis of infantile hypophosphatasia. 168 Feb 32

Linkage analysis was performed on data from Manitoba Mennonite families identified by a proband with infantile hypophosphatasia (HOPS), an autosomal recessive disorder characterized by defective skeletal mineralization. Southern blot analysis of Msp-I-digested DNA from HOPS nuclear families probed with a 2.55-kb liver/bone/kidney alkaline phosphatase (ALPL) cDNA revealed two previously undescribed RFLPs at 2.4/2.3 kb and 2.0/1.9 kb. Maximum combined lod score equals 13.25 at theta = 0. This establishes very close linkage between ALPL and HOPS and allows for the regional assignment of the HOPS gene to chromosome 1p36.1-34. Prenatal RFLP studies in an informative Mennonite family correctly predicted an unaffected fetus following chorionic villus sampling at 12 wk gestation. In addition in our Mennonite population, a nonrandom association exists between the polymorphic ALPL alleles and HOPS. These results suggest that strong linkage disequilibrium exists between HOPS and the ALPL markers. This will allow for improved carrier assignment in this high-risk population. Preliminary analysis suggests approximately 1/25 Manitoba Mennonites are HOPS carriers.
 ...
PMID:Infantile hypophosphatasia: localization within chromosome region 1p36.1-34 and prenatal diagnosis using linked DNA markers. 168 4

In the present retrospective study different dental and medical parameters have been analyzed in 17 Swedish children with established hypophosphatasia (HP). It was demonstrated that the basis for the establishment of the diagnosis varied among different dentists and physicians, and that the diagnostic parameters studied among the children varied. The most reliable parameters for HP included raised levels of phosphoethanolamine in urine, and clinical and radiologic findings associated with the legs. These findings were found among the children more often than lowered values of alkaline phosphatase in serum. Histologic analysis of an extracted tooth made a valuable diagnostic complement. It is concluded that a better diagnostic uniformity is recommended. In a well functioning collaboration with well defined tasks, both dentists and physicians can contribute to a reliable diagnosis.
 ...
PMID:Retrospective study of children with hypophosphatasia with reference to dental changes. 175 36

Prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villous sample taken in the first trimester. Very low activities of the LBK isoenzymes indicated an affected fetus. Diagnosis was confirmed at 12 weeks of gestation by measurement of LBK isoenzyme activities in fetal bone tissue. In control chorionic villous samples an inverse relation was observed between LBK and placental ALP percentage during gestational age. High LBK ALP activities are observed in decidual tissue. Chorionic villous tissue must not be sampled after 12 weeks of gestation and decidual tissue must be excluded from the sample.
 ...
PMID:First-trimester diagnosis of hypophosphatasia. Importance of gestational age and purity of CV samples. 178 79

Because defective bone mineralization occurs in hypophosphatasia (HP) and the source of bone alkaline phosphatase is the osteoblast, we investigated another marker of osteoblast activity, namely the production of osteocalcin in an HP family and controls. The mean basal osteocalcin levels in the two affected young adults and their parents (the apparent heterozygotes) were 3.4 ng/ml (range 2.5-4.6) and were not different from the levels in age- and sex-matched controls (3.6 ng/ml; range 2.5-4.6). Furthermore, the ratio of carboxylated to total osteocalcin was normal. The rise in osteocalcin after 1,25-dihydroxycholecalciferol stimulation (2 micrograms daily for one week) was slightly greater in the controls than in the HP family. These results support the concept that there is no global defect in osteoblast function in this family with HP.
 ...
PMID:Serum osteocalcin levels before and after 1,25 dihydroxy-vitamin D stimulation in a family with hypophosphatasia. 179 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>