Porphyrins fecal

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. 

If a patient presents with blisters due to photosensitivity, a plasma scan and fecal porphyrins will not only reveal the presence of a porphyria, but will also enable the distinction between the three forms that may cause such symptoms porphyria cutanea tarda (PCT), PV, and HC. Urinary porphyrins and eventually quantitative ALA und PBG in urine may be added in questionable cases or for monitoring of therapy. 

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. 

Table 7.3.5 Porphyrin standards used in the determination of fecal porphyrins by HPLC...

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]. 

Each laboratory should establish its own reference values. Those given here can only be interpreted as a guide. To our knowledge, the age dependence of fecal porphyrin excretion has not been studied. The following values for coproporphyrin I, coproporphyrin III, and protoporphyrin represent the meant two standard deviations ( 2SD) and were assessed in samples from adult volunteers <20, < 12, and < 80 nmol/g dry weight, respectively. 

Abnormal fecal porphyrins are usually specific for a porphyric condition. PCT is characterized by normal - and protoporphyrin, but with a significant isocop-... 

Fig. 7.3.4a-c Chromatograms of fecal porphyrins, (a) from a healthy individual, (b) from an individual with porphyria cutanea tarda, and from an individual with porphyria variegata (c)... 

Lim CK, Peters TJ (1984) Urine and faecal porphyrin profiles by reversed-phase high-performance liquid chromatography in the porphyrias. Clin Chim Acta 139 55-63 Minder El, Vuilleumier JP, Vonderschmitt DJ (1992) Prototype application of robot in the clinical laboratory enabling fully automated quantification of fecal porphyrins. Clin Chem 38 516-521... 

In adults, measurement of fecal nitrogen and fat in 72-hour specimens is used to assess the severity of malabsorption measurement of fecal porphyrins is occasionaEy required to characterize the type of porphyria (see Chapter 32).UsuaEy, no preservative is added to the feces, but the container should be kept refrigerated throughout the coEection period and care should be taken to prevent contamination from urine. When the collection is complete, the container and feces are weighed, and the mass of excreted feces is calculated. The specimen is homogenized and ahquotted so that the amount of fat or nitrogen excreted per... 

Sometimes the laboratory is asked to make a retrospective diagnosis of porphyria after the patient has ftiUy recovered from an attack or as the cause of a chronic neuropsychiatric disorder some time after the onset of the illness. The first step is to quantify urinary PEG screening tests are too insensitive for this purpose. Fecal porphyrin is measured... 

In PCT, excretion and plasma porphyrin concentrations return to normal during remissionj with the proportions of individual porphyrins in urine and feces remaining abnormal for longer than total porphyrin concentrations. Thus in a patient whose skin lesions have healed, and whose total urinary and fecal porphyrin concentrations are normal, determination of individual porphyrins may reveal the diagnosis. The plasma fluorescence scan in VP and fecal coproporphyrin-III excretion in HCP remain abnormal for many years after clinical remission. 

Semiquantitative Method for Total Porphyrin in Feces This simple method for total fecal porphyrins uses scanning spectrometry after extraction and is described fully on the Evolve site that accompanies this book. 

Reference values are given in Table 32-3. The expression of concentration on a dry weight basis corrects for the moisture content of feces. Total fecal porphyrin determined by this method, unlike most tests based on solvent extraction, includes uroporphyrin. 

Increased total fecal porphyrin concentration requires further investigation by fractionation, identification, and quantification of individual porphyrins using a technique, such as HPLC, that resolves coproporphyrin I and III isomers. Porphyria should never be diagnosed on the basis of raised total fecal porphyrin alone. 

The extraction method for fecal porphyrins results in some interference with the chromatography caused by a proportion of the diethyl ether dissolvmg in the aqueous phase. As a result an extra peak elutes just before the uroporphyrin position. This peak contains any uroporphyrin in the sample, up to 50% of the heptacarboxylate porphyrins and smaller amounts of hexacarboxylate and pentacarboxylate porphyrins. 

The plasma porphyrin concentration may be increased in conditions in which porphyrin excretion is impaired, such as renal failure and cholestasis. Although plasma porphyrin concentrations are usually higher in chronic renal failure with PCT than in renal failure alone, unequivocal diagnosis of PCT in this situation is best achieved by fecal porphyrin analysis or fractionation of plasma porphyrins by HPLC. ... 

Deacon AC. Fecal porphyrin screening [Letter]. Clin Chem 1990 36 1383. 

Hilt RJ, Davidson BP, van der Hooft C, Meissner DM, Meissner PN. Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of variegate porphyria precise determination of sensitivity and specificity with detection of protoporphyrinogen oxidase mutations as a reference standard. Clin Chem 2004 50 915-23. 

Rapid procedure for fecal porphyrin assay. Clin Chem 1985 31 163-7. 

Protoporphyrinogen III oxidase (EC 1.3.3.4). Ferro-chelatase activity may also be decreased. Impaired feedback inhibition of 5-aminolevulinate synthase results in excessive porphyrin production. Increased urinary porphobilinogen, 5-aminolevulinate, protoporphyrin and coproporphyrin during acute attacks. Fecal protoporphyrin and coproporphyrin constantly elevated. Fecal porphyrin-peptide conjugates increased. Mild photodermatoses clinical picture otherwise similar to that of acute intermittent porphyria. Treatment as for latter. Rare, except in white South Africans, where frequency is 0.4%. Autosomal dominant. 

In variegate porphyria, plasma is analysed for the presence of a specific fluorescence emission peak at 626 nm, that is thought to be the most sensitive test for latent mutation carrier detection besides the DNA analysis, which has just recently become available [8, 9]. In the case of hereditary coproporphyria, fecal porphyrin analysis is the best available test, but with an unknown sensitivity. Also here, there is limited experience with DNA analysis that is conducted in a few specialized laboratories recently [10]. 

Disease Urinary porphyrin precursors Urinary porphyrins Fecal porphyrin Remarks... 

CEP n All urinary porphyrin 1- All fecal porphyrin I-isomers isomers T T Uro-cosynthase activity low... 

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