Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).
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PMID:Fabry disease: a review. 1547 88

The clinical utility of most analgesic drugs is altered in the presence of patients with impaired renal or hepatic function not simply because of altered clearance of the parent drug, but also through production and accumulation of toxic or therapeutically active metabolites. Some analgesic agents may also aggravate pre-existing renal and hepatic disease. A search was performed, taking in published articles and pharmaceutical data to determine available evidence for managing acute pain effectively and safely in these two patient groups. The resulting information consisted mainly of small group pharmacokinetic studies or case reports, which included a large variation in degree of organ dysfunction. In the presence of renal impairment, those drugs which exhibit the safest pharmacological profile are alfentanil, buprenorphine, fentanyl, ketamine, paracetamol (except with compound analgesics), remifentanil and sufentanil. none of these deliver a high active metabolite load, or suffer from significantly prolonged clearance. Amitriptyline, bupivacaine, clonidine, gabapentin, hydromorphone, levobupivacaine, lignocaine, methadone, mexiletine, morphine, oxycodone and tramadol have been used in the presence of renal failure, but do require specific precautions, usually dose reduction. Aspirin, dextropropoxyphene, non-steroidal anti-inflammatory drugs and pethidine, should not be used in the presence of chronic renal failure due to the risk of significant toxicity. In the presence of hepatic impairment, most drugs are subject to significantly impaired clearance and increased oral bioavailability, but are poorly studied in the clinical setting. The agent least subject to alteration in this context is remifentanil; however the drugs' potency has other inherent dangers. Other agents must only be used with caution and close patient monitoring. Amitriptyline, carbamazepine and valproate should be avoided as the risk of fulminant hepatic failure is higher in this population, and methadone is contraindicated in the presence of severe liver disease.
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PMID:Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. 1597 13

Anderson Fabry disease (alpha galactosidase A deficiency) is an X-linked recessive lysosomal storage disorder; alpha galactosidase A deficiency results in accumulation of neutral glycosphingolipids, especially globotriaosylceramide (Gb3), in various cell types promoting development of disease with renal, cardiovascular, and cerebrovascular involvement. Clinical aspects which usually begin in childhood or adolescence include intermittent pain in the extremities (acroparesthesias), episodic "Fabry crisis" of acute pain lasting hours to days, characteristic skin lesions (angiokeratomas), hypohidrosis, heat and cold intolerance. Classic phenotype conception of the disease has changed within the past decade, recognizing that disease is not limited to the classical full-blown manifestation in affected males, but may also occur in carrier females. The expanding clinical spectrum of Anderson Fabry disease (AFD) is a real challenge to diagnosis, especially in some patients whose exclusive single organ manifestation belongs to the heart or kidney. This paper reviews natural history of three unrecognized cases recently diagnosed by markedly deficient alpha galactosidase A (alpha Gal A) activity in peripheral leucocytes. Case A: A male patient, aged 24 years, experienced recurrent acroparesthesia when he was 9 years-old. His 26 years-old sister has angiokeratomas as the only sign of disease (case B). Case C: the uncle of these two cases (A, B) has a long history of disease including chronic renal failure, bilateral deafness, stroke, aseptic osteonecrosis. The purpose of the presentation is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.
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PMID:Clinical spectrum of Anderson Fabry disease in a Romanian family. 1723