Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Myopathies encountered in uremic patients may have different pathogenetic mechanisms and treatment. Secondary hyperparathyroidism may cause uremic myopathy responding to specific treatment. This study aimed at presenting a case illustrative of the clinical features, diagnosis and management of uremic parathyroid myopathy. A 66-year old man with renal failure from membranous nephropathy developed sensory signs of uremic neuropathy and progressive painless weakness of the pelvic girdle muscles bilaterally. Motor nerve conduction velocity was normal, electromyogram was consistent with a myopathic pattern, while muscle biopsy showed a pattern of atrophy more consistent with a neuropathic pattern. Serological tests for collagen vascular diseases and hyperthyroidism were negative, while serum muscle enzymes were not elevated and serum phosphate levels were not low. Serum parathyroid hormone level was grossly elevated, while serum calcium was mildly elevated in a small fraction of the measurements, serum alkaline phosphatase showed a progressive rise and skeletal bone survey did not disclose osteopenia or signs of parathyroid bone disease. A course of calcitriol failed to improve the myopathy, which responded promptly and dramatically to parathyroidectomy. Uremic parathyroid myopathy, which has a characteristic clinical picture, must be differentiated from other neuropathic or myopathic conditions that require specific treatments. Progressive parathyroid myopathy is, by itself, an indication for parathyroidectomy, which is curative in this case.
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PMID:Severe proximal myopathy in advanced renal failure. Diagnosis and management. 1597 50

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.
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PMID:Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D. 1612 49

We report on an unusual family with an autosomal dominant limb-girdle type of myopathy and bone fragility. This family was previously reported by Henry et al. [1958] as autosomal dominant progressive limb girdle "muscular dystrophy" with propensity to fractures and defective healing of long bones. Clinical, biochemical, and radiological aspects were evaluated in eight living relatives in this family (three males and five females) and in eight deceased individuals. The average age-of-onset of the limb-girdle myopathy was 31 years occurring in 87% of affected individuals. The average age of onset of fractures was 24 years occurring in 88% of affected individuals. Biochemical analysis showed a mean alkaline phosphatase (ALP) of 64 U/L (normal 30-120) and borderline high creatine kinase (CK) of 213 U/L (normal 4-220). Radiographs revealed coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of the medullary cavity with an appearance not considered typical of Paget disease of bone (PDB) or of fibrous dysplasia. Results of nerve conduction studies were normal, and electromyograms and muscle biopsies documented non-specific myopathic changes. There is premature graying with thin hair, thin skin, hernias and the affected individuals appear older than their chronological age, and three members had a clotting disorder. Linkage analysis for markers for the chromosome 9p22.3-q12 locus indicated that the disorder in this family does not segregate with markers in the critical region of limb-girdle/inclusion body myopathy, PDB, and frontotemporal dementia (FTD) [IBMPFD, OMIM #605382]. Sequencing of Valosin-containing protein (VCP), the gene associated with IBMPFD, did not identify mutations. We have excluded linkage to the known loci for limb-girdle type of myopathy and bone disease and excluded several candidate genes. Elucidation of the novel molecular basis of this disorder may provide valuable links between bone, collagen and muscle, and targeted therapeutic options.
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PMID:Manifestations in a family with autosomal dominant bone fragility and limb-girdle myopathy. 1641 37

Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)2D3, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)2D3 and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffa's fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)2D3 were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.
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PMID:Oncogenic hypophosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1. 1823 Aug 36

Inclusion body myopathy with Paget disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD, OMIM 167320), is a progressive autosomal dominant disorder caused by mutations in the Valousin-containing protein (VCP, p97 or CDC48) gene. IBMPFD can be difficult to diagnose. We assembled data on a large set of families to illustrate the number and type of misdiagnoses that occurred. Clinical analysis of 49 affected individuals in nine families indicated that 42 (87%) of individuals had muscle disease. The majority were erroneously diagnosed with limb girdle muscular dystrophy (LGMD), facioscapular muscular dystrophy, peroneal muscular dystrophy, late adult onset distal myopathy, spinal muscular atrophy, scapuloperoneal muscular dystrophy, or amyotrophic lateral sclerosis (ALS) among others. Muscle biopsies showed rimmed vacuoles characteristic of an inclusion body myopathy in 7 of 18 patients (39%), however, inclusion body myopathy was correctly diagnosed among individuals in only families 5 and 15. Frontotemporal dementia (FTD) was diagnosed in 13 individuals (27%) at a mean age of 57 years (range 48.9-60.2 years); however, several individuals had been diagnosed with Alzheimer disease. Histopathological examination of brains of three affected individuals revealed a pattern of ubiquitin positive neuronal intranuclear inclusions and dystrophic neurites. These families expand the clinical phenotype in IBMPFD, a complex disorder caused by mutations in VCP. The presence of PDB in 28 (57%) individuals suggests that measuring serum alkaline phosphatase (ALP) activity may be a useful screen for IBMPFD in patients with myopathy.
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PMID:Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. 1826 Jan 32

The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Paget's disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Paget's disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia.
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PMID:Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus. 2011 73

Mixed connective tissue disease (MCTD) is a rheumatological disease which has to be distinguished from other entities causing inflammatory myopathy. The usual clinical presentation of inflammatory myopathy associated with connective tissue disease is not different from isolated polymyositis or dermatomyositis, i.e., subacute onset of proximal weakness affecting both upper and lower girdle with high serum CK level. Here we report a patient with MCTD/myositis overlap syndrome displaying an uncommon clinical presentation and a distribution of muscle weakness involving facial, neck and arm muscles with sparing of lower limbs. We also describe the scarcity of muscle regeneration signs on the muscle biopsy with complete absence of alkaline phosphatase positivity in the endomysial and permysial connective tissue as a novel finding of this condition.
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PMID:Mixed connective tissue disease presenting as a peculiar myositis with poor muscle regeneration. 2089 Jun 26

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a progressive, fatal genetic disorder with variable penetrance, predominantly affecting three main tissue types: muscle (IBM), bone (PDB), and brain (FTD). IBMPFD is caused by mutations in the ubiquitously expressed valosin-containing protein (VCP) gene, a member of the AAA-ATPase superfamily. The majority of individuals who develop IBM have progressive proximal muscle weakness. Muscle biopsies reveal rimmed vacuoles and inclusions that are ubiquitin- and TAR DNA binding protein-43 (TDP-43)-positive using immunohistochemistry. PDB, seen in half the individuals, is caused by overactive osteoclasts and is associated clinically with pain, elevated serum alkaline phosphatase, and X-ray findings of coarse trabeculation and sclerotic lesions. FTD diagnosed at a mean age of 55 years in a third of individuals is characterized clinically by comprehension deficits, dysnomia, dyscalculia, and social unawareness. Ubiquitin- and TDP-43-positive neuronal inclusions are also found in the brain. Genotype-phenotype correlations are difficult with marked intra-familial and inter-familial variations being seen. Varied phenotypes within families include frontotemporal dementia, amyotrophic lateral sclerosis, Parkinsonism, myotonia, cataracts, and anal incompetence, among others. Cellular and animal models indicate pathogenetic disturbances in IBMPFD tissues including altered protein degradation, autophagy pathway alterations, apoptosis, and mitochondrial dysfunction. Currently, mouse and drosophila models carrying VCP mutations provide insights into the human IBMPFD pathology and are useful as tools for preclinical studies and testing of therapeutic strategies. In this review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused by VCP mutations.
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PMID:The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. 2189 20

Blood and cloacal swabs were collected from 100 (66 female, 34 male) wild Tundra Swans (Cygnus columbianus) molting in northwestern Alaska, USA, 25-28 July 2008, to establish hematologic and serum chemistry reference values and to isolate enteric Salmonella spp. and Escherichia coli O157:H7. Plasma biochemistry and hematology values did not vary significantly by sex or age. Tundra swans had high levels of creatine kinase, lactate dehydrogenase, amylase, and alkaline phosphatase compared with some other avian species (values were up to 7 times greater), possibly indicating capture myopathy. However, concentrations were much lower (up to 8 times lower) than in other waterfowl exposed to similar or more intensive capture methods. White blood cell count and hematocrit values were similar to other waterfowl species, and enteric Salmonella spp. and E. coli O157:H7 were not present among birds sampled. Our data provide the first biochemical, hematologic, and bacteriologic reference values for wild Tundra Swans.
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PMID:Hematology, plasma chemistry, and bacteriology of wild Tundra Swans (Cygnus columbianus) in Alaska. 2224 94

Hypophosphatasia is a rare genetic disease with low tissue nonspeficic alkaline phosphatase activity (TNSALP), due to ALPL gene mutation. There are 6 clinical forms. Childhood form is caractherized by short stature, premature loss of decidous teeth and diffuse bone pain associated with a pathological bone fracture in the past. Laboratory findings present low serum level of alkaline phosphatase and high levels of serum and urinary extracelular metabolytes. It is described a case report of a 34 years old woman with previous diagnosis of childhood hypophosphatasia, caryotype 46,XX, and molecular screening for the gene ALPL with a c.1426>A p.E476K mutation, who complained of proximal muscular weakness intensified with the cold weather, exercise, and a waddling gait. The electromyography was compatible with myopathy but the muscle biopsy was normal. The serum creatine kinase levels were normal, as well as the others muscle enzymes. Clinical and laboratory/ /imaging dissociation is frequent in other metabolic bone diseases as osteomalacia. The rarity of this case of childhood hypophosphatasia with "de novo" non-progressive myopathy of the lower limbs, justified a case report with literature revision.
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PMID:Childhood hypophosphatasia with myopathy: clinical report with recent update. 2278 19


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