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)

A patient with Wilson's disease presented at the age of 41 with a neurological defect and gross osteomalacia secondary to a defect of renal tubular reabsorption. He also showed the unusual features of a renal stone in the presence of the Fanconi syndrome and a relatively low alkaline phosphatase level, possibly due to the additional inherited defect of hypophosphatasia. During four years of treatment with penicillamine and calciferol clinical improvement was spectacular. Details of amino-acid clearances before and after treatment are given, and the results suggest that, as in the brain and the liver, the function of the distal renal tubules may be restored in Wilson's disease when copper is removed.
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PMID:Effect of treatment on renal function in severe osteomalacia due to Wilson's disease. 531 32

An electrophoretic fraction of plasma alkaline phosphatase, which migrates more slowly than the main fraction, was present in one fifth of normal subjects, and in some patients with parenchymal liver disease. It was absent in patients with bone disease, uncomplicated biliary obstruction, and hepatic metastases. The electrophoretic and inhibition properties of this slow band were similar to those of intestinal phosphatase, and its significance is discussed. In a patient with hypophosphatasia this fraction was apparently not decreased.
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PMID:A distinctive fraction of alkaline phosphatase in health and disease. 591 63

Hypophosphatasia represents an inborn enzymatic deficiency characterized by a reduced activity of alkaline phosphatase in serum and tissue and an increased urinary excretion of phosphoethanolamine. 278 cases have been described until the end of 1980. Based on the age of manifestation and the predominant clinical findings the following classification is possible: The prenatal form (49 cases) with caput membranaceum, skeletal deformities and respiratory distress has a mortality of 100%. The early infantile form (94 cases) shows rickets-like osseous anomalies, dystrophy, craniostenosis, nephrocalcinosis, mortality amounting to 40%. Diagnostic features of the infantile-juvenile form (112 cases) are premature loss of deciduous teeth, bone deformities, rickets-like findings, and short stature. Mortality is only 1%. The adult form (23 cases) often remains undiscovered and has a good prognosis. It presents with pseudofractures and pains in the bones as chief symptoms. Heredity is autosomal recessive in all four types of hypophosphatasia. Possibly in the adult form there is an additional autosomal dominant inheritance. Alkaline phosphatase deficiency affects all tissues excepting the intestinal isoenzyme. Urinary excretion of phosphoethanolamine is elevated. Values for calcium and inorganic phosphorus in serum are usually normal or only slightly increased. Marked hypercalcemia is observed in severely diseased patients affected by the early infantile form. In these cases hypercalcemia often leads to nephrocalcinosis and renal insufficiency. Since alkaline phosphatase is equally active as pyrophosphatase, reduced phosphatase activity induces an accumulation of pyrophosphate in serum and its increased excretion in urine. The precise pathogenetic mechanisms of hypophosphatasia are still unknown. Possibly, the accumulation of pyrophosphate implies a disorder of calcification. Postnatal diagnosis is based on clinical findings in association with decreased alkaline phosphatase activity and increased phosphoethanolamine excretion. For the detection of heterozygotes additional biochemical markers should be tested. These include the determination of alkaline phosphatase in leucocytes and cultured skin fibroblasts, the calculation of tubular phosphate reabsorption and the analysis of pyrophosphate and pyrophosphatases. The difficulty in ascertaining the carrier state is that the measurement of a single parameter may give normal results.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Congenital hypophosphatasia]. 614 51

A 4-month-old boy with the infantile form of hypophosphatasia was followed for 9 months with measurements of serum calcium, phosphate, alkaline phosphatase and various vitamin D metabolites, together with urinary excretion of cyclic AMP. During the initial hypercalcemic stage the serum concentration of 25-hydroxyvitamin D was normal. Urinary cyclic AMP was low and the serum concentration of the dihydroxymetabolites of vitamin D were appropriate to the high serum calcium with low 1,25-(OH)2D and relatively high 24,25(OH)2D and 25,26(OH)2D levels. Due to restrictions of the vitamin D intake and lack of exposure to sun he developed vitamin D-deficiency rickets at 9 months of age with very low serum concentration of 25-hydroxyvitamin D and markedly increased urinary excretion of cyclic AMP. Following vitamin D treatment the serum level of 1,25(OH)2D showed a brisk rise to a considerably elevated value. Initially the serum concentration of alkaline phosphatase was well below the normal range, rose markedly during the stage of active rickets and returned to the characteristic low levels of hypophosphatasia with healing of the rickets.
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PMID:Vitamin D metabolism in hypophosphatasia. 629 16

A 7-year-old boy was referred to the children's hospital because of gross oedema and tiredness. Massive proteinuria was found and the condition was diagnosed as a childhood nephrotic syndrome. Concomitantly, pathologically low levels of serum alkaline phosphatase were recorded, and this, together with generalized osteoporosis and premature synostosis of cranial sutures, led to a second diagnosis: hypophosphatasia. The patient's family history further confirmed this condition of a heritable defect of metabolism. Dental inspection revealed very carious teeth with characteristically enlarged pulp chambers in molars. Histological examination of an extracted tooth revealed an unusually wide zone of predentine with some other dentinal irregularities. No cement layer was found. The skeletal age and exfoliation of primary teeth, however, were normal, unlike most reported cases of hypophosphatasia. The patient's renal disease was treated mainly with corticosteroids. There is no treatment for hypophosphatasia.
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PMID:Cranial manifestations of hypophosphatasia in childhood nephrotic syndrome. 643 Aug 33

After biochemical and radiographic studies, enzyme replacement therapy in three patients with the infantile form of hypophosphatasia was attempted by weekly intravenous infusions of bone alkaline phosphatase-rich (BAP) plasma from patients with Paget bone disease. Subsequently, circulating BAP activity was substantially increased in each patient, and in one was maintained in the normal range for nearly 2 months. Despite partial or complete correction of the deficiency of circulating BAP activity, we observed no radiographic evidence for arrest of progressive osteopenia or improvement in rachitic defects in any of the patients. Failure of infants with hypophosphatasia to show significant healing of rickets on correction of circulating BAP activity supports the hypothesis that this isoenzyme functions in situ during normal skeletal mineralization.
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PMID:Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusions of alkaline phosphatase-rich Paget plasma: results in three additional patients. 650 42

This article presents detailed clinical and laboratory investigations of six hypophosphatasia kindreds. Serum alkaline phosphatase and urinary phosphoethanolamine comparisons between the affected population and a normal control population demonstrate these parameters routinely identify the heterozygous individual when age and sex variations are accounted for. Using clinical data from the kindred population and a detailed review of the literature, the type and frequency of clinical findings for both the homozygous and heterozygous genotype are enumerated. The clinical and biochemical phenotypes were subjected to segregation analysis. When the results of these analyses are viewed in light of their mathematical limitations and the genetic precepts of autosomal dominant and recessive inheritance, hypophosphatasia is best described as an autosomal dominant disorder with 85% penetrance and homozygous lethality.
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PMID:Clinical, laboratory, and genetic investigations of hypophosphatasia: support for autosomal dominant inheritance with homozygous lethality. 664 50

Histochemical and direct enzyme analysis of osseous tissue from 23 patients with hypophosphatasia revealed that all clinical forms of this inherited metabolic bone disease are characterized by deficiency of alkaline phosphatase (ALP) activity in bone. The severe infantile form has the most profound deficiency, infantile form has the most profound deficiency, yet the cellular source of this enzyme--osteoblasts and their matrix vesicles--are normal by routine light and electron microscopy. Despite radiographic changes in bone metaphyses consistent with rickets, iliac crest biopsy of one affected child revealed no abnormalities; the other had evidence of a mineralization defect, but not as severe as that in affected infants. In this child and several affected adults with osteomalacia, osteoblasts appeared flat and metabolically inactive. Although these histological changes suggested a different pathogenetic mechanism for adult and childhood hypophosphatasia, these changes are most likely secondary to the underlying osteomalacia. Our findings are most consistent with evidence that childhood and adult hypophosphatasia often represent clinical expression of the heterozygous state for ALP deficiency which, when homozygous, results in the clinically severe, recessive, infantile form. Histochemical and direct analysis of bone tissue from controls and patients with hypophosphatasia demonstrated that the severe infantile form is associated with the most severe ALP deficiency. In the milder clinical forms, ALP deficiency in bone is not as profound. In general, the severity of the clinical expression of hypophosphatasia reflects the magnitude of the deficiency of ALP in bone. This is the expected finding for this inborn error of metabolism, which illustrates the major role bone ALP activity has in the process of normal skeletal mineralization.
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PMID:Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. 669 Aug 84

Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient. Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase. The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered. The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogeneous disorder which includes both severe and clinically mild forms.
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PMID:Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family. 672 76

Infantile hypophosphatasia is a rare inborn error of metabolism in which the expression of the liver/kidney/bone locus of the alkaline phosphatase gene is defective. Analysis of tissues from a suspected case of hypophosphatasia for alkaline phosphatase activity demonstrated very low levels of activity in liver, kidney, and rib as compared to tissues from a case of osteogenesis imperfecta or normal adult tissues. Intestinal and placental tissues demonstrated significant levels of activity. Gene-specific amino acid inhibitors and isoelectric focusing demonstrated that the activity which was present in the liver, kidney, and rib tissues from the case of hypophosphatasia was of the intestinal type and not the normal liver/kidney/bone form of the enzyme.
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PMID:Isoenzymes of alkaline phosphatase in infantile hypophosphatasia. 685 32


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