Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical symptoms and laboratory findings were assessed in three women with acute intermittent porphyria. After 15 days of pharmacologic washout and free diet (time 0), the patients were give a well balanced normocaloric diet for 7 days (time 1), followed by 7 days of high carbohydrate normocaloric diet (time 2); on days 15 to 21 (time 3) well balanced normocaloric diet was given, and finally on days 22 to 28 (time 4) to the well balanced normocaloric diet cimetidine (0.4 g twice daily) was added. On days 3, 5, and 7 of times 1-4 the following porphyrin precursors were determined: ALA, PBG, total uroporphyrin, total coproporphyrin, and total porphyrin. At times 1 and 3, high values were found while levels dropped to normal during times 2 and 4. During times 1 and 3, patients complained of headache, insomnia and anxiety; during time 2, all patients complained of anxiety and only one suffered from insomnia. Finally, during time 4, all patients had only slight anxiety. Untoward effects of cimetidine were not observed in any of the patients.
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PMID:[Clinical and laboratory findings concerning at first dietary and afterwards cimetidine treatment of acute intermittent porphyria]. 795 57

The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes. This deficiency leads to de-repression of the first and normally rate-controlling enzyme of the heme synthetic pathway, delta- or 5-aminolevulinic acid [ALA] synthase-1, and thus to marked up-regulation of this key enzyme and to marked hepatic overproduction of ALA. In addition, except for ADP, there is marked overproduction as well of porphobilinogen [PBG], the intermediate immediately downstream of ALA in the synthetic chain, and, especially in HCP and VP, also porphyrinogens and porphyrins farther down the pathway. The major clinical features of the acute porphyrias are attacks of severe neuropathic-type pain. Pain is felt first and foremost in the abdomen but may also occur in the back, chest, and extremities. Attacks are more common in women than in men [ratio of about 4:1], often accompanied by nausea, vomiting, constipation, tachycardia, and arterial hypertension. Hyponatremia may also occur. Some patients also describe chronic symptoms of pain, anxiety, insomnia, and others.
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PMID:Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs). 3098 16