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)

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

The experience of 30 porphyric crisis is reviewed in 25 patients attended since 1967: 21 patients had 1 crisis, 3 had 2, and 1 had 3 of these episodes. In all patients, porphyria was diagnosed in relation to one crisis, even though many of them had family histories and/or previous clinical symptoms of this disease. There was clear predominance (80%) of women, but they are also a majority among acute porphyrias. The most frequent symptoms were: abdominal pain, tachycardia, dark urine, neurological and psychiatric alterations and arterial hypertension. The neurological alterations required the use of a respirator in 9 crisis (33%), which was maintained in 2 patients during 4 months. In 6 crisis (20%) there were no neurological symptoms. Among laboratory tests, hyponatremia was notable for its frequency (53.4%) and intensity. Increase in urinary porphobilinogen, a requirement for diagnosis, between 15 and 130 times the normal value was observed. Septic complications, such as pneumonia, septicemia, and urinary infection, were frequent (50%). Factors suspicious of triggering crisis episodes were: drugs, usually more than 2, in 50% of the cases; pregnancy in 30% of the women and in a lesser proportion, intense exercise, and surgery. In 10 patients, crisis triggering factors were not identified or informed. The role of pregnancy, childbirth delivery or puerperium in causing a crisis is not clear, because the patients who had a crisis related to them had 15 other pregnancies without incidents; besides, in the pregnancy which was accompanied by a crisis, there was always one or more than one potentially triggering drug present. The first therapeutic step was oral and/or parenteral administration of an overload of carbohydrates and, if there was no response, intravenous infusion of hematin was prescribed. Four (13.3%) patients died even though they had received hematin, but it had been administered too late due to a delay in diagnosis. In surviving patients, there were no organic sequels of any kind.
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PMID:[Porphyric crisis: experience of 30 episodes]. 1034 14

Historical evidence has been collected attempting to diagnose members of royal houses, perhaps most publicized by Macalpine and Hunter (1969) for George III and his assumed porphyria, claiming that his insanity was a classic case of thereof. This rare metabolic disease presents with a variety of signs and symptoms: skin disease, abdominal pain, tachycardia, and neuro-psychiatric findings. The porphyrias are hereditary and since George III and Frederick William I share ancestors it seemed reasonable to investigate if the latter may also have suffered from porphyria. The pathography of both kings is meticulous, showing for both that abdominal pain, erratic behavior, restlessness, and discolored urine were frequently observed and complete recovery interictally was common. Intercurrent illnesses, fasting, alcohol and even tobacco smoking have been shown to be inducers of attacks and these risk factors are well documented in royal history.--The diagnosis of porphyria was not recognized then and other names were used, such as Cachexia hypochondriaca, Asthma spasmodico flatulentum, dolores arthritici.--We propose that Frederick William I suffered from an inducible porphyria.
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PMID:[Friedrich Wilhelm I and porphyria]. 1047 52

Porphyrias are inherited defects of heme synthesis with manifestations that can mimic surgical diseases; they can be provoked by administration of certain drugs. Manifestations such as abdominal pain, vomiting, tachycardia, hypertension, neuropathy, fever, confusion, and seizures have been described. Management of patients with porphyria is designed to avoid triggering drugs, such as barbiturates, and perhaps, benzodiazepines and ketamines. Nontriggering drugs should be used in the management of patients with porphyria. Because starvation can induce an attack, glucose infusions are important in the prevention and treatment of porphyria.
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PMID:Anesthetic considerations in hepatic porphyrias. 1050 4

Acute intermittent porphyria (AIP) is the most common type of hepatic acute porphyria. In this work, we have analyzed the biochemical data of all Argentinean AIP families studied in the Porphyrins and Porphyrias Research Centre (CIPYP). We have shown that: (i) the prevalence for this population is about 1:125,000; (ii) the disease is more frequent in women than in men (7:3); (iii) about 60% are latent carriers; (iv) 15% of patients with symptomatic AIP died during an acute attack; (v) the most important precipitating factors of acute attacks in our population were the ingestion of therapeutic drugs (25%), anesthetics in surgical interventions (25%) and infections (20%); (vi) the initial symptom in Argentinean AIP individuals is severe abdominal pain (100%), and it is often accompanied by constipation (37%), anorexia (37%) and tachycardia (30%); and (vii) the percentage of recurrence of the acute attacks is high (81%).
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PMID:Acute intermittent porphyria: biochemical and clinical analysis in the Argentinean population. 1052 59

Porphyrias are the result of inherited enzymatic defects of the heme's biosynthesis chain. A porphyria crisis with abdominal pain and neurological or psychiatric signs may be precipitated by drugs. Our purpose is to list the main drugs which may precipitate phorphyria crisis, specifying which are contraindicated such as cefalosporins, anaesthetics, anti epileptic and anti tubercular drugs, and which are doubtful because of conflicting results published in literature. In any case it is necessary to verify any prescription before giving a drug to a patient with porphyria.
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PMID:[Porphyria and drugs]. 1199 30

A fatal case of acute intermittent porphyria in a 22 years old Indian male is reported. He presented with abdominal pain and constipation, subsequently developed status epilepticus, acute respiratory failure and quadriparesis. He succumbed to the illness on the twelfth day. Among the neuromuscular causes of acute respiratory failure, requiring ventilatory support, porphyria is a condition potentially treatable, but rarely suspected.
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PMID:Acute intermittent porphyria as a cause of acute respiratory failure. 1220 44

The characteristic symptoms for acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Usually there is an exogenous or endogenous factor inhibiting the heme biosynthesis or increasing the consumption of heme produced in already decreased amount. The most important precipitating factors are the therapeutic drugs. Therefore, certain therapeutic drugs ordered for carriers or patients with acute porphyria are serious risk factors. It is very important to identify patients and carriers with acute porphyria as early as possible and to make a close follow-up so the development of the symptoms of the life threatening acute attack could be prevented. It is very difficult to suspect the diagnosis of acute porphyria. There is a very characteristic discrepancy between the serious complaints and the actual clinical findings. The severe cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs and sensory loss are the main signs at the beginning. The specific symptoms which help to establish the diagnosis--red-colored urine, hyponatremia, tachycardia, hypertension, subileus, acute psychosis, gradually developing paresis of the lower and then the upper limbs--are characteristic for the later phase of the acute attack. Very often there is a rapid progression with Landry-type paralysis developing in days or even in hours, following respiratory paralysis or serious arrhythmia is the cause of the death. In case of suspicion of acute porphyria the patient should be directed to a department where the specific laboratory methods--measurement of the porphyrin precursors, porphyrins and their isomers in urine and feces, quantitation of protoporphyrin in red blood cells, measurement of the plasma porphyrin and enzyme activity--to diagnose the different types of the disease and the immediate specific treatment with heme arginate are possible if needed. All of these are available in the National Porphyria Center.
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PMID:[Acute porphyrias in differential diagnosis]. 1276 67

Acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types of them: acute intermittent porphyria, porphyria variegata, coproporphyria and delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of their frequency. Basically the clinical picture is the same in the four types of acute porphyria. The most frequent complaints and symptoms are: cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the advanced phase, there is a red-colored urine, hyponatremia, subileus, acute psychosis and Landry-type paralysis. Without proper treatment death is caused by respiratory paralysis or serious arrhythmia. In case of suspicion of acute porphyria it is mandatory to identify the type of the acute porphyria and the actual status of the patient. The later indicates what kind of treatment should be used. In the acute phase the early therapy with heme arginate is the treatment of choice. Since the clinical symptoms are precipitated by endogenous or exogenous inducing factors--most often by drugs-, the drugs negatively affecting the heme biosynthesis should be omitted at once even in the suspicion of acute porphyria. The role of the inducing factors in the manifestation of the clinical symptoms makes possible the prevention. It is possible to avoid the inducing factors and this way to prevent the acute attack if the acute porphyrias are recognized in time and the patients and the carriers are under regular control. The patients receive special identification card and the up-to-date list of safe drugs. They can use only these drugs in any kind of illness. Other drugs should be considered as porphyrinogenic since it is impossible to predict based on their chemical structure if they negatively affect the heme biosynthesis.
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PMID:[Treatment of acute porphyrias. The importance of follow-up of patients and carriers]. 1280 70


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