Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncologic emergencies can occur at any time during the course of a malignancy, from the presenting symptom to end-stage disease. Although some of these conditions are related to cancer therapy, they are by no means confined to the period of initial diagnosis and active treatment. In the setting of recurrent malignancy, these events can occur years after the surveillance of a cancer patient has been appropriately transferred from a medical oncologist to a primary care provider. As such, awareness of a patient's cancer history and its possible complications forms an important part of any clinician's knowledge base. Prompt identification of and intervention in these emergencies can prolong survival and improve quality of life, even in the setting of terminal illness. This article reviews hypercalcemia, hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac tamponade, superior vena cava syndrome, neutropenic fever, spinal cord compression, increased intracranial pressure, seizures, hyperviscosity syndrome, leukostasis, and airway obstruction in patients with malignancies. Chemotherapeutic emergencies are also addressed.
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PMID:Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment. 2185 93

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure.
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PMID:Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia, and pseudotumor cerebri: case report. 2239 3

We report a case of 26-year-old man treated for ectopic mediastinal parathyroid adenoma with videoassisted thoracic surgery and perioperative methylene blue intravenous injection. The patient had elevated serum calcium levels, and a history of recurrent urinary stone seizures from 8 years ago. Hypercalcemiadue to the hyperparathyroidism was suspected and am ectopic parathyroid adenoma in the mediastinum was identified by computed tomography (CT) and magnetic resonance imaging(MRI).Thoracoscopic extirpation of mediastinal parathyroid adenoma was scheduled with the help of tumor staining by methylene blue intravenous injection. The lesion was identified easily during surgery, andthe thoracoscopic surgery could be safely performed. The postoperative course is well, and hypercalcemia was improved. The ureteral stone seizures did not occur subsequently.
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PMID:[Ectopic mediastinal parathyroid adenoma resected by video-assisted thoracic surgery with intraoperative methylene blue infusion]. 2344 43

Hypophosphatasia (HPP) is a rare metabolic disease with the hallmark finding of deficient serum tissue nonspecific alkaline phosphatase (TNSALP) activity. TNSALP is primarily known for its role in mineralization; hence, HPP is characterized by defective mineralization of bone and/or teeth. TNSALP is also necessary for proper vitamin B6 metabolism and its participation as a cofactor for neurotransmitters in the central nervous system. Defective TNSALP activity in the brain can result in intractable seizures responsive to pyridoxine. The pathophysiology of pyridoxine-responsive seizures (PRS) in severe HPP remains to be clearly defined. We review the case of a 2-month-old Caucasian boy presenting with seizures refractory to conventional antiepileptic medications. Empiric treatment with favorable response to pyridoxine in conjunction with severe metabolic bone disease, extremely low serum alkaline phosphatase, elevated phosphoethanolamine, hypercalcemia, hypercalciuria, and nephrocalcinosis led to a clinical diagnosis of infantile HPP. Sequence analysis revealed compound heterozygosity of the TNSALP gene with a novel mutation in exon 9 and a previously reported mutation in exon 12. This case reminds the physician that severe infantile HPP can present with PRS as its major initial manifestation and should alert clinicians to consider HPP in their differential of PRS. In addition, despite this severe genotype, the clinical diagnosis of our patient was delayed because of minimal phenotypic features initially. This highlights that the phenotype-genotype correlation could be variable even in severe disease. This case also demonstrates that HPP should be classified as PRS and not a form of pyridoxine-dependent epilepsy (PDE) as our patient was able to stop the pyridoxine supplementation without seizure recurrence once enzyme replacement was initiated. With the advent of enzyme replacement therapy, this once fatal disease may have improved morbidity and mortality.
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PMID:Infantile hypophosphatasia secondary to a novel compound heterozygous mutation presenting with pyridoxine-responsive seizures. 2347 1

Maternal primary hyperparathyroidism causing hypercalcemia during pregnancy can suppress fetal and neonatal parathyroid hormone secretion. We report a newborn with transient hypoparathyroidism presented by hypocalcemic seizure and tetany on the 21st postnatal day in whom the final diagnosis was asymptomatic maternal primary hyperparathyroidism. Neonatal hypocalcemia usually occurs early in life in infants of maternal primary hyperparathyroidism, and although it is very rare, further investigation for unexplained late-onset hypocalcemia may reveal this diagnosis.
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PMID:Late neonatal hypocalcemic tetany as a manifestation of unrecognized maternal primary hyperparathyroidism. 2429 40

Posterior reversible encephalopathy syndrome (PRES) is characterised by headache, visual disorders, seizures, altered mentation, consciousness disturbances and focal neurological signs. Initially described in patients with pre and eclampsia, severe hypertension, posterior reversible encephalopathy syndrome can occur in other clinical conditions such as infection, sepsis, shock, cancer chemotherapy, autoimmune diseases and hypercalcemia. Pathogenesis of brain lesions in PRES is not full understood and two opposite theories have been proposed. Both models are based on the central role of hypertension. According to the first theory, hypertension could cause a breakdown of the autoregulatory system in cerebral circulation, leading to brain edema. The second theory suggests that hypertension causes activation of autoregulatory system, which finally results in a vasoconstriction of brain vessels with hypoperfusion, ischemia and subsequent fluid leakage. However a large number of patients, with PRES, doesn't show hypertension. We here describe the hypothesis of the crucial role of endothelial dysfunction and activation in PRES pathogenesis. Our hypothesis offers a common pathogenetic mechanism in which every PRES-related condition can be set. In our model, the activation of immune system and the consequent endothelial activation start a molecular cascade which finally causes the production of molecules which alter the normal homeostasis of blood-brain barrier. This alteration consists in a weakening of brain vessel tight junctions, which allows fluid leakage and edema. In this scenario, hypertension would be an epiphenomenon of the underlying mechanism and not the cause and, for this reason, it can be present or not in PRES.
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PMID:Posterior reversible encephalopathy syndrome: the endothelial hypotheses. 2461 35

Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) in the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). The disease has been classified according to patient age when the first signs and symptoms manifest; i.e., perinatal, infantile, childhood, adult HPP. Other types include odonto HPP and perinatal benign. Babies with the perinatal/infantile forms of HPP often die with severe rickets and respiratory insufficiency and sometimes hypercalcemia and vitamin B6-responsive seizures. The primary biochemical defect in HPP is a deficiency of TNAP activity that leads to elevated circulating levels of substrates, in particular inorganic pyrophosphate (PPi), a potent calcification inhibitor. To-date, the management of HPP has been essentially symptomatic or orthopedic. However, enzyme replacement therapy with mineral-targeting TNAP (sALP-FcD10, also known as ENB-0040 or asfotase alfa) has shown promising results in a mouse model of HPP (Alpl-/- mice). Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acellular cementum, and enamel defects in this model of severe HPP. Clinical trials using mineral-targeting TNAP in children 3 years of age or younger with life-threatening HPP was associated with healing of the skeletal manifestations of HPP as well as improved respiratory and motor function. Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. Enzyme replacement therapy with asfotase alfa has to-date been successful in patients with life-threatening HPP.
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PMID:Hypophosphatasia - pathophysiology and treatment. 2525 37

Hypercalcaemia in neonates is rare and often asymptomatic, but can have significant morbidity. If severe, it can cause symptoms including irritability, vomiting and seizures. We present the case of a baby girl, born at term after a traumatic delivery, who developed severe hypercalcaemia with nephrocalcinosis. She had several large areas of subcutaneous fat necrosis following delivery, with prolonged low-level elevation of C reactive protein. Subcutaneous fat necrosis of the newborn is a rare and underdiagnosed condition, often accompanied by high plasma calcium. Although self-limiting, it is important to recognise and treat this condition to minimise kidney damage, and to avoid unnecessary investigations or treatment with long courses of antibiotics. The infant recovered well, although a degree of nephrocalcinosis remains.
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PMID:Subcutaneous fat necrosis causing neonatal hypercalcaemia. 2617 96

Hypophosphatasia is the inborn error of metabolism characterized by low serum alkaline phosphatase activity (hypophosphatasaemia). This biochemical hallmark reflects loss-of-function mutations within the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a cell-surface homodimeric phosphohydrolase that is richly expressed in the skeleton, liver, kidney and developing teeth. In hypophosphatasia, extracellular accumulation of TNSALP natural substrates includes inorganic pyrophosphate, an inhibitor of mineralization, which explains the dento-osseous and arthritic complications featuring tooth loss, rickets or osteomalacia, and calcific arthopathies. Severely affected infants sometimes also have hypercalcaemia and hyperphosphataemia due to the blocked entry of minerals into the skeleton, and pyridoxine-dependent seizures from insufficient extracellular hydrolysis of pyridoxal 5'-phosphate, the major circulating form of vitamin B6, required for neurotransmitter synthesis. Autosomal recessive or dominant inheritance from ~300 predominantly missense ALPL (also known as TNSALP) mutations largely accounts for the remarkably broad-ranging expressivity of hypophosphatasia. High serum concentrations of pyridoxal 5'-phosphate represent a sensitive and specific biochemical marker for hypophosphatasia. Also, phosphoethanolamine levels are usually elevated in serum and urine, though less reliably for diagnosis. TNSALP mutation detection is important for recurrence risk assessment and prenatal diagnosis. Diagnosing paediatric hypophosphatasia is aided by pathognomic radiographic changes when the skeletal disease is severe. Hypophosphatasia was the last type of rickets or osteomalacia to await a medical treatment. Now, significant successes for severely affected paediatric patients are recognized using asfotase alfa, a bone-targeted recombinant TNSALP.
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PMID:Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. 2689 60

Hypophosphatasia is a rare disorder due to a mutation in the ALPL gene encoding the alkaline phosphatase (ALP) leading to a diminished activity of the enzyme in bone, liver, and kidney. Hypophosphatasia is a heterogeneous disease, ranging from extreme life-threatening forms revealed at birth in young infants presenting with severely impaired bone mineralization, seizures, and hypercalcemia, to young adults with premature exfoliation of their teeth without any other symptom. We will review the challenges of the clinical, biochemical, radiological, and genetic diagnosis. Schematically, the diagnosis relies on low ALP levels and, in most cases, on the genetic defect in the ALPL gene. An enzyme replacement therapy is now developed for hypophosphatasia; early results in the severe form of the disease are extremely encouraging. However, multidisciplinary care remains the core of treatment of hypophosphatasia encompassing nutritional support, adjustment of calcium and phosphate intake, monitoring of vitamin D levels, careful and personalized physical therapy, and regular dental monitoring and care.
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PMID:Hypophosphatasia. 2708 88


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