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)

Among many metabolic disorders, porphyrias and Fabry disease are known to affect autonomic nervous system. In patients with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, autonomic symptoms such as abdominal pain, vomiting, hypertension and tachycardia are among the most prominent clinical manifestations. Fabry disease is clinically characterized by severe limb pain, hypohidrosis, angiokeratomas and various autonomic symptoms. In both porphyrias and Fabry disease, pathological changes in the central and peripheral autonomic nervous system have been documented. In porphyrias, a loss of myelinated fibers, axonal degeneration, and segmental demyelination in peripheral autonomic nerves as well as chromatolysis of several brain stem nuclei have been found. In Fabry disease, abnormal amount of the substrates of alpha-galactosidase, i.e. ceramide di- and trihexoside, are found to be accumulated in the central and peripheral autonomic nerves.
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PMID:[Autonomic dysfunction in metabolic diseases]. 161 65

The porphyrias can be grouped conveniently by their presenting symptoms. Acute intermittent neurological symptoms of neuritis, abdominal pain and psychoses may occur in acute intermittent porphyria, hereditary coproporphyria and variegata porphyria. Increase of the porphyrin precursors delta-aminolaevulinic acid and porphobilinogen may be observed in the urine during attacks (Watson-Schwartz test). Patients with acute symptoms of photosensitivity with burning pain and oedema within short exposure periods may have erythropoietic protoporphyria, with high erythrocyte and stool protoporphyrins, erythropoietic coproporphyria, and in the last few years of life the more recently described hepatoerythropoietic porphyria. Symptoms of chronic photosensitivity include; hyperpigmentation, hypertrichosis, easy fragility of the skin with bullae and subsequent scarring in porphyria cutanea tarda (PCT), with increased uroporphyrin in the urine and stool; variegate porphyria with increased protoporphyrin and coproporphyrin in the stool; congenital erythropoietic porphyria with an increased copro- and uroporphyrin (isomer I) in the erythrocytes, urine and stool; and hepatoerythropoietic porphyria in later life, in which the chronic features are similar to PCT. In 1913 Meyer-Betz injected himself with 200 mg haematoporphyrin. Initially, at the higher levels, the symptoms were those of solar urticaria as observed in erythropoietic porphyria, but after several months became identical to PCT. A comparison of quantitative porphyrin analysis (performed on 323 patients with porphyria) and chromatography provides additional confirmation for the diagnosis.
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PMID:Porphyria: genetic and acquired. 329 37

A patient with familial variegate porphyria is described. She was admitted in an acute attack and developed severe dysautonomia manifested clinically by postural hypotension, tachycardia and constipation with severe abdominal pain. Whilst formal testing of autonomic function demonstrated the presence of marked abnormalities, peripheral nerve conduction studies were normal.
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PMID:An acute attack of variegate porphyria complicated by severe autonomic neuropathy. 694 85

Hereditary coproporphyria (Hepatic coproporphyria: HCP); HCP is the rarest and least recognized among hepatic porphyrias and is characterised by an excess of faecal and urinary excretion of coproporphyrin (mainly isomer III). The deficiency is in coproporphyrinogen oxidase. HCP was first described by Berger and Goldberg in 1955 and was considered an asymptomatic biochemical abnormality. It later became evident that HCP could provoke acute attacks similar to those of acute intermittent porphyria (AIP) and variegate porphyria (VP). Such episodes are often provoked by barbiturates, sulphonamides and other drugs, and include automatic symptoms (hypertension, tachycardia, abdominal pain, constipation), central (epileptic seizures, mental disturbances) and peripheral nervous system dysfunction. During acute attacks, urinary ALA (delta-aminole-vulinic acid) and PBG (porphobilinogen) are elevated just as in AIP and VP, however, a marked elevation of faecal COPRO (coproporphyrin) is diagnostic of HCP. Laparoscopic finding of our case showed a map-like appearance of the liver surface with slightly depressed dark-bluish areas and reddish-brown areas. The liver biopsy specimen showed red fluorescence under ultraviolet light. On HE staining, hydropic degeneration of the hepatocytes and many brown granules in the hepatocytes were seen. A part of the granules stained positive for iron. Schmorl's stain showed many needle-shaped crystallines. Erythropoietic coproporphyria (ECP); Heilmeyer and Clotten have described that elevated PROTO (protoporphyrin) and COPRO were found in the RBC of the patient. Topi et al. described two brothers with cutaneous photosensitivity similar to that of erythropoietic protoporphyria, but with elevated RBC PROTO and COPRO III in both. Very little is known about this disease.
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PMID:[Hereditary coproporphyria (Hepatic coproporphyria), Erythropoietic coproporphyria]. 761 59

A 23-year-old man with epilepsy and a past history of abdominal pain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated. Electrophysiologic studies demonstrated a peripheral neuropathy with features of axonal degeneration and demyelination. Axonal degeneration was documented by sural nerve biopsy. Markedly elevated urinary delta-aminolevulinic acid and porphobilinogen indicated a diagnosis of acute porphyria. Other laboratory studies were most consistent with hereditary coproporphyria. Motor function improved considerably but incompletely over 1 year. An acute, primarily motor neuropathy can occur in several forms of porphyria, including acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria, sometimes even in the absence of concomitant gastrointestinal symptoms.
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PMID:Acute peripheral neuropathy due to hereditary coproporphyria. 800 8

Severe hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are hereditary diseases. Each type of porphyria is the result of a specific decrease in the activity of one of the enzymes of heme biosynthesis. Acute attacks are very serious: the abdominal pains are severe and the neurological manifestations can lead to death or incomplete recovery with irreversible sequelae (usually paralysis). Since 1985, the prognosis of acute attacks has been greatly improved by the introduction of heme-arginate. The 69 acute attacks (30 patients, 4 men and 26 women) that we treated with heme-arginate between 1988 and 1991 are described in this report. All patients were infused with 250 mg/d of heme-arginate for 4 days: the mean duration of abdominal pain was 2.5 days (SD 0.72). For 95 p. 100 of the attacks, the total hospitalization time was 5 days or less; side effects were very minor. In every case, a favorable response was dependent upon the early initiation of heme therapy.
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PMID:[Acute attacks of hepatic porphyria: specific treatment with heme arginate]. 836 99

Variegate porphyria (VP), a low-penetrant autosomal dominant inherited disorder of haem metabolism, is characterised by photosensitivity (Fig. 1) and a propensity to develop acute neuropsychiatric attacks with abdominal pain, vomiting, constipation, tachycardia, hypertension, psychiatric symptoms and, in the worst cases, quadriplegia. Acute attacks, often precipitated by inappropriate drug therapy, are potentially fatal. While earlier workers thought the distal haem biosynthetic enzyme ferrochelatase may be involved in the genesis of VP, it was shown in the early 1980's, and is now accepted, that VP is associated with decreased protoporphyrinogen oxidase activity (PPO) (E.C.1.3.3.4). VP prevalence is much higher in South Africa than elsewhere; probably due to a founder effect with patients descending from a 17th century Dutch immigrant. PPO cDNAs from Bacillus subtilis, Myxococcus xanthus, human placenta and mouse liver have been cloned, sequenced and expressed. Human and mouse cDNAs consist of open reading frames 1431 nucleotides long, encoding a 477 amino acid protein. The human PPO gene contains thirteen exons, spanning approximately 4.5 kb. We have identified a C to T transition in codon 59 (in exon 3) resulting in an arginine to tryptophan substitution (R59W). A protein expressed from an in vitro-mutagenized PPO construct exhibits substantially less activity than the wild type. The R59W mutation was present in 43 of 45 patients with VP from 26 of 27 South African families investigated, but not in 34 unaffected relatives or 9 unrelated British patients with PPO deficiency. Since at least one of these families is descended from the founder of South African VP, this defect may represent the founder gene defect associated causally with VP in South Africa.
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PMID:A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. 867 6

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

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

Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria and variegate porphyria--are characterized by episodic acute attacks that consist of various neuro-psychiatric symptoms and signs, such as abdominal pain, vomiting, constipation, hypertension and tachycardia associated with increased excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is manifested as pain in the extremities, and it may progress to a severe motor neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis during acute attacks. Attacks are often induced by precipitating factors such as drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they should be eliminated when a patient is treated during an attack. Heme, the end biosynthetic product, is the most effective therapy for restoration of porphyrin biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days. Adequate calories are necessary and parenteral nutrition with carbohydrates may be necessary. Attacks may also require therapy for hypertension, pain and epileptic seizures. Strict avoidance of all precipitating factors may not be necessary in the asymptomatic phase.
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PMID:Management of the acute porphyrias. 963 23


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