Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a retrospective study covering 411 acute intermittent porphyria patients, four cases of a coincidence with Crohn's disease or ulcerative colitis were found. Their courses of disease confirmed that patients with chronic inflammatory bowel disease have a higher risk for acute porphyria manifestation. Both malnutrition (glycopenic induction) and sulphasalazine (drug-induced exacerbation) are known as triggering factors for acute porphyric states. Furthermore, diagnosis of acute intermittent porphyria tends to be much more difficult in such cases, as the acute phases of abdominal pain are likely to be associated with the enteral disease process. A delay of diagnosis and therapy of acute hepatic porphyria, however, may endanger the patient by pareses, which could be irreversible or even lethal. Therefore, whenever there is suspicion of a coinciding acute porphyria, urinary screening tests for porphyria should immediately be performed and, if a coinciding acute hepatic porphyria is diagnosed, porphyrogenic drugs like sulphasalazine should be avoided in treatment of chronic inflammatory bowel disease.
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PMID:Manifestation of acute intermittent porphyria in patients with chronic inflammatory bowel disease. 177 36

Patients with acute hepatic porphyria present with abdominal pain and neurologic abnormalities. Although the disease is uncommon, the emergency physician will occasionally encounter a patient with porphyria. The relevant pathophysiology of acute hepatic porphyria and the treatment of the patient with acute hepatic porphyria are reviewed.
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PMID:Acute porphyria in the emergency department. 266 71

Acute intermittent porphyria is a genetic hepatic porphyria characterized by acute gastrointestinal and neurological symptoms, and accompanied by excess excretion of delta-aminolevulinic acid and porphobilinogen. Here, we report a case of acute intermittent porphyria with attacks of abdominal pain, an elevated serum thyroxine level, and hypercholesterolemia with an increased level of high-density lipoprotein-cholesterol concentration. The diagnosis of acute intermittent porphyria was confirmed by a high urinary excretion of porphobilinogen and a low level of erythrocyte hydroxymethylbilane synthase activity. After being treated with a high carbohydrate intake and propranolol, the patient improved gradually during the following 3 weeks. The patient remained asymptomatic during the 6-month follow-up period. The serum thyroxin and cholesterol levels returned to normal 6 months later. In conclusion, we suggest that for any patient who presents with unexplained abdominal pain, abnormal thyroid function and hypercholesterolemia, a simple Watson-Schwartz urine test should be performed for the screening of acute intermittent porphyria. If the Watson-Schwartz test is positive, the erythrocyte hydroxymethylbilane synthase activity should be determined to confirm the diagnosis of acute intermittent porphyria.
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PMID:Abnormal thyroid function and hypercholesterolemia in a case of acute intermittent porphyria. 280 66

The effectiveness of 2 hematins administered by intravenous infusion was compared in acute intermittent porphyria. Judging from subjective symptoms (abdominal pain), clinical improvement was complete and constant. There was a rapid decrease in urinary excretion of porphyrins precursors, with a clearer response of delta-aminolevulinic acid than of porphobilinogen. Urine levels of uroporphyrin often returned to normal after two infusions. The drugs were very well tolerated. Provided it is administered early, before neurological complications develop, treatment with hematin completely relieves abdominal symptoms and suppresses most of the biochemical changes associated with hepatic porphyria.
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PMID:[Acute attacks of hepatic porphyria. Treatment with hematin. 5 cases]. 294 13

Hepatic porphyrias are characterized by neurological symptoms manifested by abdominal pain, neuropathies and mental aberrations. Porphyrins are ubiquitous and essential biochemical constituents of living beings acting as mediators of oxidation reaction in the metabolism of the steroid, drugs, environmental chemicals or as a mean of exchanging gases, such as oxygen and carbon dioxide between the environment and the tissue of the body using endogenous polypeptide properties. The different porphyrins arising from the arrangement of normal heme synthesis are characterized by an accumulation and excretion of specific intermediate porphyrins and/or of precursors exerting toxic effect, initiating cascades of generations of polypeptides, neurotransmitters and gut-brain axis peptide responsible for the symptoms of clinical status. We studied polypeptide levels in 27 patients (19 females, 8 males) presenting acute attack of hepatic porphyria: 2 with ALA dehydratase-deficient porphyria; 9 with acute intermittent porphyria; 12 with porphyria cutanea tarda and 4 with variegate porphyria. During acute attacks of porphyria, polypeptides were found to be constantly increased: vasoactive intestinal polypeptide (VIP); neurotensin (NT); substance P; pancreatic polypeptide; gastrin-releasing peptide; gastrin and motilin. Administration of the somatostatin (antagonizing polypeptide), which was undetectable or low before treatment, apparently alleviated the acute symptomatology. Elevated levels of polypeptides, at least partly, contribute to appearance of acute symptoms in porphyria patients.
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PMID:Polypeptide levels increase during acute onset of hepatic porphyrias. 907 85

A distressingly common occurrence is the erroneous diagnosis of hepatic porphyria in patients with chronic abdominal pain in which either urinary porphyrins are elevated and/or Watson-Schwarz test is positive. This work investigates a characteristic case and points at possible pitfalls in establishing a diagnosis. In the patient described, spot urine analysis showed positive Watson-Schwarz test and increased porphyrins at three separate occasions, while normal values of precursors and porphyrins were recorded in 24-hrs. urinary collections during four hospitalization periods for acute abdominal pain. Various colorimetric and HPLC methods employed excluded the diagnosis of porphyria and led to resolving the discrepancy between home and hospital results. It was found that the false increase in porphyrins in the spot samples emerged from a substance present in yeast tablets which the patient was consuming. The positive Watson-Schwarz test obtained was probably the result of the fact that the urine samples were concentrated with creatinine values exceeding 400 mg%. The case reported above, as well as studies carried out in three healthy volunteers and in an AIP patient, led to the conclusion that in order to obtain reliable result, 24-hrs. urinary collections should be examined, rather than spot urine samples.
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PMID:Yeast, creatinine and false diagnosis of porphyria. 907 92

Porphyrias, a group of inborn errors of heme synthesis, are classified as hepatic or erythropoietic according to clinical data and the main site of expression of the specific enzymatic defect. Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by deficient activity of coproporphyrinogen III oxidase (COX). Typical clinical manifestations of the disease are acute attacks of neurological dysfunction; skin photosensitivity may also be present. We report a variant form of HC characterized by a unifying syndrome in which hematologic disorders predominate: harderoporphyria. Harderoporphyric patients exhibit jaundice, severe chronic hemolytic anemia of early onset associated with hepatosplenomegaly, and skin photosensitivity. Neither abdominal pain nor neuropsychiatric symptoms are observed. COX activity is markedly decreased. In a first harderoporphyric family, with three affected siblings, a homozygous K404E mutation has been previously characterized. In the present study, molecular investigations in a second family with neonatal hemolytic anemia and harderoporphyria revealed two heterozygous point mutations in the COX gene. One allele bore the missense mutation K404E previously described. The second allele bore an A-->G transition at the third position of the donor splice site in intron 6. This new COX gene mutation resulted in exon 6 skipping and the absence of functional protein production. In contrast with other COX gene defects that produce the classical hepatic porphyria presentation, our data suggest that the K404E substitution (either in the homozygous or compound heterozygous state associated with a mutation leading to the absence of functional mRNA or protein) is responsible for the specific hematologic clinical manifestations of harderoporphyria.
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PMID:Neonatal hemolytic anemia due to inherited harderoporphyria: clinical characteristics and molecular basis. 945 77

Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.
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PMID:Acute porphyrias: pathogenesis of neurological manifestations. 951 77

Acute intermittent porphyria (AIP), an inborn error of metabolism, results from the deficient activity of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD). Clinical symptoms of this autosomal dominant hepatic porphyria include episodic acute attacks of abdominal pain, neuropathy, and psychiatric disturbances. Current therapy based on intravenous heme administration is palliative and there is no way to prevent the attacks. Thus, efforts are focused on methods to replace the deficient activity in the liver to prevent the acute attacks of this hepatic porphyria. Here we explore the efficiency of a non-viral gene delivery to obtain PBGD expression in the liver of AIP transgenic mice. Four vectors were evaluated: naked DNA and DNA complexed to liposomes, polyethylenimine (PEI), and PEI-galactose, using a luciferase construct as reporter gene. The vectors were administered intravenously or directly into the portal vein with transient blood flow blockage. After tail vein injection of the DNA complexes, the liposome vector had the highest luciferase expression in lung and less in liver. When injected into the portal vein, the naked DNA had considerably higher hepatic reporter gene expression; 100 microg of naked DNA had the highest hepatic luciferase expression 24h after portal vein injection. When these vectors were used to deliver the PBGD gene into the AIP mouse model no enhancement of the endogenous PBGD activity in liver was detectable, despite the presence of the PBGD-plasmids as verified by PCR. Thus, more efficient non-viral vectors are needed to express sufficient PBGD activity over the endogenous hepatic level (approximately 30% of normal) in this murine system.
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PMID:Non-viral delivery of the porphobilinogen deaminase cDNA into a mouse model of acute intermittent porphyria. 1511 Mar 17

The article presents diagnostic problems concerning the case of 54-year old woman with a delayed diagnosis of a severe attack of acute intermittent porphyria (AIP), which on admission manifested mainly as flaccid quadriplegia. The signs of neurological deficit were accompanied by changes in electrocardiographic recording that suggested acute myocardial ischaemia without apparent chest pain. Based upon a detailed history and identification of potential factors that might have triggered the attack the suspicion of acute hepatic porphyria was raised. The suspicion was confirmed by biochemical testing in the Institute of Hematology and Transfusiology in Warsaw. The treatment with glucose was administered, drugs contraindicated in porphyria were excluded, and early rehabilitation programme was instituted, which led to a marked improvement of general status and resolution of quadriplegia after 16 weeks. Parallel to the improvement of neurological status and a decrease in urinary excretion of heme precursors the normalisation of ECG changes was observed. The authors point out that differential diagnosis of abdominal pain with concomitant hyponatraemia should include an attack of acute porphyria since early administration of proper management prevents the development of life-threatening neurological signs accompanying the severe attack. The diagnosis of an attack of acute porphyria in the phase of predominant neurological signs, in the absence of abdominal pain, may be difficult and always warrants, apart from anamnestic data, the confirmation with appropriate biochemical testing.
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PMID:[Late diagnosis of a severe attack of acute intermittent porphyria (AIP)--diagnostic dilemmas]. 1572 92


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