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)

We report on a 43-year-old patient with short stature (hyposomia), allegedly the result of vitamin-D-resistant rickets, previously treated for ankylosing spondylitis. In addition, a uricostatic drug therapy was also necessary because of hyperuricemia with gout attacks. Further examinations revealed the accurate diagnosis: Rathbun's disease. Hypophosphatasia is a hereditary disorder characterized by a deficiency of liver/bone/kidney alkaline phosphatase activity in serum and tissues with defective bone mineralization, bone deformities, short stature, early loss of teeth, and craniosynostosis. In our patient radiographic features were spinal hyperostosis, but with syndesmophytes, chondrocalcinosis of peripheral joints and intervertebral discs, calcific periarthritis and premature closure of skull sutures. Curved ribs and short stature were suggestive of rickets. The aim of this case report is to demonstrate the close relations between hypophosphatasia and spondylitis ankylosans in respect to radiology and clinical symptoms.
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PMID:[Rathbun syndrome (hypophosphatasia). Clinical aspects: dwarfism and Bechterew symptoms]. 179 58

We have carried out first-trimester prenatal diagnosis of hypophosphatasia in 16 pregnancies with a 1 in 4 risk of this condition. The liver/bone/kidney isoenzyme of alkaline phosphatase was measured in chorionic villus samples using a specific monoclonal antibody and an enzymatic amplification system. Fifteen of the 16 pregnancies were correctly predicted, while one has been lost to follow up. We suggest that this assay system is likely to be superior to DNA-base methods for the first-trimester prenatal diagnosis of hypophosphatasia.
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PMID:First-trimester prenatal diagnosis of hypophosphatasia: experience with 16 cases. 192 79

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization, deficiency of alkaline phosphatase (ALP) activity, increased excretion of phosphoethanolamine (PEA) in the urine and premature loss of the deciduous teeth. A male hypophosphatasia patient aged 15 years 6 months, with premature exfoliation of the deciduous teeth and manifesting severe periodontal destruction in the permanent dentition, was examined. Antibody titers against seven strains by the enzyme-linked immunosorbent assay (ELISA), monocyte and neutrophil chemotaxis studies and cellular immunity tests were performed. Low levels of ALP in serum and PEA in the urine were found. Radiographic examination showed a similar pattern of alveolar bone loss to that of the localized juvenile periodontitis. Suppressed monocyte and neutrophil chemotaxis were not detected. Slightly depressed CD2+, CD3+ and CD4+ and slightly elevated activity of NK cells were found. An elevated level of antibody to Porphyromonas gingivalis was observed and this antibody titer was decreased by periodontal treatments. The affected sites of the patient showed resistance to conventional periodontal therapy. P. gingivalis was estimated to associate as an important pathogen in the etiology of periodontal destruction in this hypophosphatasia patient in addition to the dental abnormalities such as abnormal enamel, dentin, or cementum formation.
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PMID:[A case of severe periodontal disease in adolescence associated with hypophosphatasia]. 195 7

We measured plasma levels of pyridoxal-5'-phosphate (PLP), a cofactor form of vitamin B6 and apparent natural substrate for alkaline phosphatase (ALP), in carriers and in non-carriers of the severe perinatal and infantile forms of hypophosphatasia, both before and after an oral load of pyridoxine (i.e. 1/3 mg/kg body weight). The assignment of carrier status was determined by serum ALP activity, level of serum inorganic phosphate, and if necessary urinary phosphoethanolamine excretion. Plasma PLP levels were significantly increased in the carriers both before and especially after B6 loading.
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PMID:Increased plasma pyridoxal-5'-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia. 207 38

To clarify its physiologic role, alkaline phosphatase (ALP) was examined in normal skin fibroblasts and was shown to be the tissue-nonspecific (TNS) isoenzyme type (as evidenced by heat and inhibition profiles) and to be active toward millimolar concentrations of the putative natural substrates phosphoethanolamine (PEA) and pyridoxal-5'-phosphate (PLP). Fibroblast ALP has a low-affinity activity, with a distinctly alkaline pH optimum (9.3), toward 4-methylumbelliferyl phosphate (4-MUP), PEA, and PLP but a more physiologic pH optimum (8.3) toward physiologic concentrations (micromolar) of PEA and PLP. Normal fibroblast ALP is linked to the outside of the plasma membrane, since in intact cell monolayers (1) dephosphorylation rates of the membrane-impermeable substrates PEA and PLP in the medium at physiologic pH were similar to those observed with disrupted cell monolayers, (2) brief exposure to acidic medium resulted in greater than 90% inactivation of the total ALP activity, and (3) digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) released about 80% of the ALP activity. Hypophosphatasia fibroblasts were markedly deficient (2%-5% control values) in alkaline and physiologic ALP activity when 4-MUP, PLP, and PEA were used as substrate. The majority of the detectable ALP activity, however, appeared to be properly lipid anchored in ecto-orientation. Thus, our findings of genetic deficiency of PEA- and PLP-phosphatase activity in hypophosphatasia fibroblasts, as well as our biochemical findings, indicate that TNS-ALP acts physiologically as a lipid-anchored PEA and PLP ectophosphatase.
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PMID:Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. 222 Aug 17

Twenty obligate carriers of infantile hypophosphatasia (HOPS), a severe autosomal recessive metabolic bone disorder, were studied and compared with 36 controls. Decreased serum alkaline phosphatase activity and increased urinary phosphoethanolamine excretion were confirmed in the HOPS carriers. Relative hyperphosphatemia was documented for the first time in the carriers. Logistic regression analysis was used to develop models for the diagnosis of and screening for HOPS carriers in the high-risk population of Manitoba Mennonites. Models based on serum alkaline phosphatase activity and on serum phosphate levels with or without urinary phosphoethanolamine excretion were used for diagnostic purposes. A model based on serum alkaline phosphatase activity and on the serum phosphate level was the most suitable for screening.
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PMID:Hyperphosphatemia in infantile hypophosphatasia: implications for carrier diagnosis and screening. 230 98

Hypophosphatasia, a rare heritable form of rickets/osteomalacia, is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequence of either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5 1/2 years and has had a much milder clinical course. Although consanguinity is absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are consistent with heterozygosity in each parent. Fibroblast ALP activity is less than 1% normal in all 3 patients with no complementation observed in heterokaryon analysis. Accordingly, the genetic defects appear to be identical in all 3 patients. Our findings show that infantile hypophosphatasia may be inherited as an AR condition where there is variable expressivity and that homozygosity or compound heterozygosity, as may be the case in this family, is not necessarily lethal.
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PMID:Infantile hypophosphatasia: autosomal recessive transmission to two related sibships. 233 3

We have determined the activity of alkaline phosphatase in chorionic villous tissue obtained in the first trimester of pregnancy, in order to obtain the normal range of values as a prerequisite for application to the prenatal diagnosis of the rare bone disease hypophosphatasia. The activities found were a combination of intestinal and liver/bone/kidney types; traces of placental type were present in only one sample.
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PMID:Activities of alkaline phosphatase in first trimester chorion biopsy tissue. 241 34

Hypophosphatasia is a hereditary disease characterized by congenital deficiency of tissue alkaline phosphatase. One of its dental features is the shedding of teeth. We have experienced a case which was referred to our clinic with the chief complaints of loss and shedding of lower deciduous central incisors and was diagnosed to be highly suspected of hypophosphatasia as a result of hematological examination at the pediatric clinic. As a result of close systemic and dental examination and further study of changes in the course for two and a half years, the following findings were obtained: 1. Low serum alkaline phosphatase level and hypercalcemia were the systemic findings of the disease. 2. There was no delayed ossification in terms of carpal bone age. 3. X-ray cephalography revealed no particular cephalic abnormality, except the lack of development of frontalis and mandibular. 4. Dental findings comprised marked resorption of upper alveolar bone in the front teeth area and pronounced instability of front deciduous teeth. 5. As for changes in oral symptoms, extraction of A because of pronounced instability was followed by spontaneous shedding of A. About one year later, A was extracted because of marked instability. At the time of this writing, A was slightly instable without any abnormality in the other teeth. 6. Pathohistological study of the extracted teeth disclosed only a little resorption of cement of root apex and dysgonic periodontium without any marked tissue changes.
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PMID:[Dental study of hypophosphatasic child]. 248 52

Hypophosphatasia is a heritable disorder characterized by defective osteogenesis and deficient liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. Severe forms of the disease are inherited in an autosomal recessive fashion. We examined cultured skin fibroblasts from twelve patients with severe hypophosphatasia. All were deficient in L/B/K ALP activity, yet produced normal levels of the corresponding mRNA. Sequence analysis of L/B/K ALP cDNA isolated from one of the patient-derived fibroblast lines revealed a point mutation that converted amino acid 162 of mature L/B/K ALP from alanine to threonine. The patient was homozygous and the parents, who are second cousins, heterozygous for this mutation. Introduction of the mutation into an otherwise normal cDNA disrupted the expression of active enzyme, demonstrating that a defect in the L/B/K ALP gene resulted in hypophosphatasia and that the enzyme is, therefore, essential for normal skeletal mineralization.
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PMID:First identification of a gene defect for hypophosphatasia: evidence that alkaline phosphatase acts in skeletal mineralization. 260 56


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