Porphyria acute

Acute porphyria Do not use clarithromycin in combination with ranitidine bismuth citrate in patients with a history of acute porphyria. 

Atsmon A, Blum I. Treatment of acute porphyria variegata with propranolol. Lancet 1970 24 196-197. 

The types of test to be performed depend on the clinical situation. If the patient has an acute, severe disease and an acute porphyria is suspected, PBG should be assessed either qualitatively by a reliable screening test or quantitatively in a spot urine. Quantitative ALA can be added to uncover lead intoxication, which may be clinically undistinguishable from an acute porphyria. Furthermore, the extremely rare ALAD deficiency may show normal PBG. If increased values of PBG are present, urinary porphyrins can be determined to confirm the existence of porphyria. 

If the patient is actually asymptomatic, but has a family history of acute porphyria or prior symptoms suspicious of acute porphyria, hydroxymethylbilane synthase (HMBS) activity, plasma scanning, and fecal porphyrins should be measured. These tests will reveal AIP, P V, and HC. As a small percentage of AIP families exhibit normal HMBS activity, PBG in a urine sample can be added. PBG determination can also performed as a first choice, if an acute porphyria is suspected. But if normal, it does not exclude acute porphyrias in asymptomatic phases. Furthermore, the existence of an acute porphyria is only proved if the value exceeds at least five times the upper limit of normal. 

Typical pathological values show a strong pink color. Other colors should not be interpreted. Values elevated at least fivefold are proof of acute porphyria. Lower, but still increased values may be encountered in asymptomatic porphyria patients and as a secondary phenomenon due to alcohol intake or stress. PBG elevation is apparently more specific for porphyria. 

All acute porphyrias show similar urinary porphyrin patterns with predominant elevation of uroporphyrin and coproporphyrin III isomer in addition, hepta-, hexa-, and especially pentacarboxyporphyrins are increased (see Fig. 7.3.3). 

Fecal porphyrin analysis is useful to differentiate between the three acute porphyrias and to positively diagnose HC. In addition, it may support the diagnosis of PCT and of erythropoietic protoporphyria. 

Fecal porphyrins are determined to differentiate between the three acute porphyrias, AIP, PV, and HC (Table 7.3.1). Symptomatic PV shows abundant fecal coproporphyrins, whereby the III isomer is always dominant and protoporphyrin is elevated. In symptomatic HC, only fecal coproporphyrins with dominance of the III isomers are increased. Fecal porphyrins are usually normal in AIP. They may be moderately elevated in acute porphyric attacks in AIP, but coproporphyrin I is then higher than coproporphyrin III isomer [11]. 

E1MBS activity is lowered in AIP. In the case of a newly diagnosed acute porphyria, determination of HMBS activity enables the diagnosis of AIP. We further use it in AIP family screening combined with mutation analysis. 

Sandberg S, Elder GH (2004) Diagnosing acute porphyrias. Clin Chem 50 803-805... 

Flufenamate is not recommended in patients with acute porphyria and was associated with a case of acute proctocolitis (Ravi et al., 1986). 

Treatment During acute porphyria attacks, patients require medical support, particularly treatment for pain and vomiting. The severity of symptoms of the porphyrias can be diminished by intravenous injection of hemin, which decreases the synthe sis of ALA synthase. Avoidance of sunlight and ingestion of j P-carotene (a free-radical scavenger) are also helpful. 

What may be the first case in which an attack of acute porphyria was triggered by gonadotrophic stimulation of the ovary has been reported (17). 

Horgan P, Jones H. Olanzapine use in acute porphyria. Int J Psychiatry Clin Pract 2003 7 67-9. 

The catabolism of haemoglobin yields haem, which is subsequently converted to bilirubin in a two-step process that takes place in the hepatocyte. First, the microsomal enzyme haem oxygenase cleaves the porphyrin ring of haem, generating biliverdin in an energy-utilising reaction. Following this, biliverdin is converted to bilirubin by the cytosolic enzyme biliverdin reductase. As the liver is the active site for biosynthesis of porphyrin and haem, deficiencies in some enzymes of the porphyrin pathway may lead to insufficient haem production and an increase in porphyrin levels, which causes acute porphyria attacks. 

The greatest care in prescribing for these patients is required if serious illness is to be avoided. Patients (1 in 10 000 UK population) are so highly vulnerable that lists of drugs known or believed to be unsafe are available, e.g. in the British National Formulary. Additionally, we provide a table of drugs considered safe for use in the acute porphyrias at the time of publication (Table 8.2). The list is revised... 

Review Molecular pathogenesis of hepatic acute porphyrias. J. Gastroenterol. Hepatol. 1996 11 1046-1052... 

Kauppinen, R., Mustajoki, R Acute porphyria and hepatocellular carcinoma. Brit. J. Cancer 1988 57 117 — 120... 

Antidotes e. g. silibinin against Amanita poisoning or N-acetylcysteine in paracetamol intoxication, haemarginate in acute porphyria Primary iiver therapeutics e. g. penicillamine, glucocorticoids, azathioprine, interferon-a, aimed at primary intervention in the aetiology or pathomechanism of liver disease. 

The requirements for successfully treating clinically manifest acute porphyria are (7.) elimination of the... 

Laiwah AC, Brodie Ml, Goldberg A. Carbamazepine-induced non-hereditary acute porphyria. Lancet 1983 1(8339) 1442. 

Acute porphyriasis may be exacerbated chlorpropamide was considered to be unsafe in patients with acute porphyria as it has been associated with acute attacks (Moore et al., 1987). Tolazamide was considered to be unsafe in patients with acute porphyria because it has been shown to be por-phyrinogenic in animals and in vitro systems (Moore et al., 1987). 

In Table 32-4 the porphyrias are divided into the acute porphyrias, in which acute neurovisceral attacks occur, and the nonacute porphyrias. Other classifications include division into hepatic (acute intermittent porphyria (AIP], hereditary coproporphyria [HOP], variegate porphyria [VP], and PCT) and erythropoietic (congenital erythropoietic porphyria [CEP], erytliropoietic protoporphyria [EPP]) porphyrias according to the main site of overproduction of... 

The acute porphyrias include ALA dehydratase deficiency porphyria (ADP), AIP, VP, and HCP. These disorders are autosomal dominant except for ADP, which is autosomal recessive. 

All the autosomal dominant acute porphyrias show extensive allelic heterogeneity. More than 200... 

About 25% of patients with overt acute porphyria have no family history of the disease. Such sporadic presentation is a reflection of the high prevalence of mutations in the population acute porphyria caused by de novo mutation is uncommon. 

Unlike the other acute porphyrias, ADP is an autosomal recessive disorder. Patients are compound heterozygotes or... 

Data from Elder GH, Hift RJ. Treatment of acute porphyria. Hosp Med 2001 62 422-8. 

Long-term complications of acute porphyria include chronic renal failure, hypertension, and hepatocellular car-... 

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