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)

Mutations in the calcium-sensing receptor gene (CaSR) may result in disorders of calcium homeostasis manifesting as familial benign hypocalciuric hypercalcaemia (FBHH), neonatal severe hyperparathyroidism (NSHPT) or autosomal dominant hypocalcaemia with hypercalciuria (ADHH). FBHH may have a population prevalence as high as one in 16 000, and ADHH one in 70 000. NSHPT is very rare. The FBHH condition is usually asymptomatic. Parathyroidectomy does not result in normal serum calcium, and no active treatment is indicated. To differentiate FBHH from primary hyperparathyroidism (PHPT), a guideline which includes measurement of serum calcium, intact parathyroid hormone (PTH), magnesium and fasting urinary calcium excretion is proposed. Screening of family members for hypercalcaemia, and occasionally a search for mutations in the CaSR gene, may be required. The NSHPT condition may manifest with hypercalcaemia, (usually) very elevated serum PTH concentration, subperiosteal erosions and fractures. Milder cases may be managed medically, but respiratory failure, extreme hypercalcaemia and failure to thrive are indications for early parathyroidectomy. The ADHH condition may result in asymptomatic hypocalcaemia, but some affected family members have minor symptoms, and a minority experience seizures in infancy which can recur into adulthood. A significant proportion of cases previously reported as idiopathic hypoparathyroidism (IHP) may in fact be due to mutations in the CaSR gene. In a moderately hypocalcaemic patient with no other clearly discernible cause, an elevated urine calcium:creatinine ratio is suggestive of ADHH, as is the presence of a first-degree relative with hypocalcaemia. If treatment with vitamin D analogues is undertaken, serum and urine calcium should be monitored, advice which applies equally to ADHH and IHP.
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PMID:Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. 1558 33

The authors describe a 9-year-old girl with precursor-B acute lymphoblastic leukemia (ALL) who presented with dehydration and severe hypercalcemia. She had received oral vitamin D and calcium supplementation for 4 days, the last dose 48 hours prior to admission, and required pediatric intensive care unit (PICU) hospitalization for management of the hypercalcemia and safe initiation of induction chemotherapy. Her clinical course was complicated by pancreatitis, disseminated intravascular coagulation, pleural effusion, and focal seizures. Although the exact mechanism of hypercalcemia was not elucidated, it was likely related to the underlying ALL, without dismissing the prior vitamin D and calcium supplementation as a possible contributing factor. The hypercalcemia resolved with specific antileukemic therapy along with supportive care and administration of calcitonin. Hypercalcemia is an uncommon metabolic abnormality in children with ALL, but it can be life-threatening. Children with ALL should be referred to tertiary-care institutions with PICU and subspecialty support because serious metabolic and other complications can occur before or after the administration of chemotherapy.
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PMID:Life-threatening hypercalcemia complicated by pancreatitis in a child with acute lymphoblastic leukemia. 1589 68

A reversible syndrome of headache, altered mental status, seizures and cerebral visual abnormalities with neuroradiological studies suggesting predominantly posterior white matter abnormalities has been described. This syndrome has been referred to as posterior reversible encephalopathic syndrome (PRES). PRES has been associated with hypertensive encephalopathy, eclampsia and treatment with immunosuppressive or cytotoxic agents. Rare case reports describe association with hypercalcemia. We present a patient with AIDS, Mycobacterium avium intracellulare related hypercalcemia with posterior reversible encephalopathic syndrome.
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PMID:Posterior reversible encephalopathic syndrome due to severe hypercalcemia in AIDS. 1601 20

(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. The optimal dose seems to range from 30 to 180 mg/day and varies widely from one patient to another. (4) 3 double-blind placebo-controlled trials, lasting for a maximum of one year and involving a total of 1136 dialysis patients with chronic renal failure, showed no improvement in quality of life with cinacalcet. The target parathormone level was reached by 40% of patients on cinacalcet versus 5% of patients on placebo, while the effects of cinacalcet on calcium levels (-7%) and phosphate levels (-8%) were modest. No impact on bone complications is mentioned in available reports. (5) The assessment of treatment of parathyroid cancer is limited to one ongoing non comparative trial involving 21 patients. (6) During clinical trials, 11% of dialysis patients had low parathormone levels, creating a risk of adynamic bone disease and fractures, but available data are sparse. (7) Two-thirds of patients receiving cinacalcet have episodes of hypocalcaemia, which may in part account for reports of seizures (1.4% of patients), nausea (31%) and vomiting (27%). Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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PMID:Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data? 1676 95

Pyridoxine-responsive seizures (PRS) and the role of pyridoxine (PN, vitamin B(6)) in hypophosphatasia (HPP) are incompletely understood. Typically, PRS and HPP are rare, independent, metabolic disorders. In PRS, seizures resist standard anticonvulsants apart from PN, yet have a good prognosis. In HPP, inactivation of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP) impairs skeletal mineralization and causes rickets in infants that can be fatal. Here, we report a 7-month-old girl, newly diagnosed with infantile HPP, who presented as a neonate with PRS but without bony abnormalities. Analysis of biogenic amines in cerebrospinal fluid (CSF) suggested brain pyridoxal 5'-phosphate (PLP) deficiency, although PLP in CSF was not decreased. She had normal cognitive milestones but failure to thrive and rickets. Nearly undetectable serum ALP activity, elevated plasma PLP and urinary phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi) levels, hypercalcemia, hypercalciuria and nephrocalcinosis were consistent with infantile HPP. Only prednisolone reduced serum calcium levels. Despite improved growth and weight gain, she developed rib fractures and died from respiratory failure at age 9 months. Sequence analysis of the TNSALP gene revealed novel missense mutations in exon 7 (c.677T>C, p.M226T) and exon 10 (c.1112C>T, p.T371I). Our patient demonstrated that PRS in neonates may not necessarily be "idiopathic"; instead, such seizures can be caused by severe HPP that becomes clinically apparent later in infancy. The pathophysiology of PRS in HPP differs from the three other genetic defects known to cause PRS, but all may lead to brain PLP deficiency reducing seizure thresholds. All reported HPP patients with neonatal seizures died within 18 months of birth, suggesting that PRS is an indicator of HPP severity and lethal prognosis. We recommend that assessment of any neonate with PRS should include measurement of serum ALP activity.
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PMID:Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. 1739 61

Seizures induced by hypercalcemia are rare. A few case reports of seizures associated with hypercalcemia have been published, but none due to the milk alkali syndrome. This is the first report regarding seizures associated with calcium carbonate overuse. The two patients described in this article, who had no risk factors for developing epilepsy, suffered from status epilepticus probably induced by hypercalcemia. Subsequently, they both developed complex partial seizures, and were later found to have mesial temporal sclerosis on MRI. There are no reports linking hypercalcemia to mesial temporal sclerosis. While this may be a coincidence, there is reason to suspect that the development of persistent epilepsy, possibly due to mesial temporal sclerosis, was caused by prolonged seizures induced by hypercalcemia.
Seizure 2008 Apr
PMID:Mesial temporal sclerosis after status epilepticus due to milk alkali syndrome. 1780 61

Physician reporting of lapses of consciousness (LOC) to the Department of Motor Vehicles is a controversial topic in medicine. The objective of this study was to describe current LOC reporting practices by emergency physicians (EPs) in a state with mandatory reporting requirements (California). A questionnaire describing 14 different clinical scenarios involving LOC was distributed to a diverse sample of California EPs. Clinical scenarios included new seizure, hypoglycemia, atrial fibrillation/rapid heart rate, cerebrovascular accident, micturation syncope, vasovagal syncope, hepatic encephalopathy, alcohol intoxication, closed head injury, hyperosmolar coma, methamphetamine psychosis, dementia, hyperventilation syndrome, and hypercalcemia. Emergency physicians were asked how often they would report these LOC-related conditions to the state. Simple summary statistics were calculated. The response rate was 207/340 (61%) of the forms distributed. The average number of years in Emergency Medicine practice among respondents was 12 (range 1-35), and 57% were Emergency Medicine trained. Of the 14 scenarios, only one (new-onset seizure) was reported frequently by EPs (89% reported "nearly always" or "most of the time"). The remaining 13 scenarios were rarely reported (mean of 86% for "occasionally" or "never"). Although reporting of LOC, from any cause, is mandatory in California, only new-onset seizures are frequently reported by California EPs.
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PMID:Reporting patterns for "lapses of consciousness" by California emergency physicians. 1820 38

Subcutaneous fat necrosis in a newborn is a rare, benign and self-limiting panniculitis. Hypercalcemia may develop and has been implicated as the cause of serious complications including seizures, nephrocalcinosis, and death. We report a case of subcutaneous fat necrosis in a newborn associated with asymptomatic and uncomplicated hypercalcemia, which resolved spontaneously.
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PMID:Subcutaneous fat necrosis in a newborn associated with asymptomatic and uncomplicated hypercalcemia. 1941 78

The calcium-sensing receptor (CASR) is expressed in parathyroid hormone (PTH)-secreting cells of the parathyroid gland and cells lining the renal tubule. The activated CASR modulates intracellular signaling pathways altering PTH secretion and renal cation and water handling. Inherited abnormalities of the CASR gene give rise to a variety of disorders of mineral ion homeostasis. Heterozygous loss-of-function mutations cause familial (benign) hypocalciuric hypercalcemia (FHH) in which the lifelong mild hypercalcemia is generally asymptomatic. Homozygous inactivating mutations give rise to neonatal severe hyperparathyroidism (NSHPT) with extreme hypercalcemia and marked skeletal changes. Heterozygous activating mutations of the CASR cause autosomal dominant hypocalcemia (ADH) that may be asymptomatic or present with seizures in the neonatal period or childhood or later in life. Phenocopies of FHH or ADH are due to circulating CASR inactivating or activating autoantibodies, respectively. The CASR is the target of small molecule allosteric modifiers, either activators, calcimimetics, or inhibitors, calcilytics.
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PMID:Calcium-sensing receptor and associated diseases. 2037 33

Milk-alkali syndrome is mainly caused by the ingestion of large amounts of calcium and absorbable alkali. This syndrome can lead to metastatic calcification, renal failure and metabolic alkalosis secondary to hypercalcemia. Hypercalcemia is rarely a cause of seizure activity. Very few case reports have been published linking seizure to hypercalcemia, but only one recent case report about mesial temporal sclerosis relates the seizure activity to Milk-alkali syndrome. This is another report regarding seizure associated with excess calcium carbonate intake, but without any evidence of mesial temporal sclerosis. The patient described in this article, suffered from status epilepticus most likely secondary to hypercalcemia. Evaluations for malignancy, thyroid, and parathyroid dysfunctions were non conclusive, therefore hypercalcemia in our patient was attributed to milk-alkali syndrome given the history of the prolonged calcium carbonate intake.
Seizure 2011 Oct
PMID:Status epilepticus secondary to milk-alkali syndrome induced by hypercalcemia (oral antacids). 2151 51


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