Porphyria urine

Porphyria Urine PBG/ALA Urine Porphyrins Fecai Porphyrins Erythrocyte Porphyrins Plasma Fluorescence Emission Peak... 

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Late porphyria, as a rule, is accompanied by swelling of the liver, its abnormal functioning, change in color of urine to dark-orange. 

May show port-wine urine during episode Other porphyrias mainly cutaneous symptoms... 

There are a large number of hereditary or acquired disturbances of porphyrin synthesis, known as porphyrias, some of which can cause severe clinical pictures. Several of these diseases lead to the excretion of heme precursors in feces or urine, giving them a dark red color. Accumulation of porphyrins in the skin can also occur, and exposure to light then causes disfiguring, poorly healing blisters. Neurological disturbances are also common in the porphyrias. 

Caution [B (D if near term), M] Contra Sulfonamide or salicylate sensitivity, porphyria, GI/GU obst avoid in hepatic impair Disp Tabs SE GI upset discolors urine dizziness, HA, photosens, oligospermia, anemias, Stevens-Johnson synd Interactions T Effects OF oral anticoagulants, oral hypoglycemics, MTX, pheny-toin, zidovudine X effects W/ antibiotics X effects OF digoxin, folic acid, Fe, procaine, proparacaine, sulfonylureas, tetracaine EMS T Effects of anticoagulants monitor EGG and BP for signs of hypovolemia and electrolyte disturbances d/t D skin urine may become yellow-orange may stain contact lenses T risk of photosensitivity Rxns OD May cause NA, drowsiness, HA, abd pain, skin Rxns, lactic acidosis, and jaundice symptomatic and supportive... 

For idiosyncratic, patient related adverse reactions, less confirmatory tests are available but the number is growing. Skin, blood and urine tests are available to confirm acute and chronic allergic reactions. Genetic tests can determine the susceptibility of individuals and includes general tests such as for the porphyrias and sickle cell anaemia, and specific tests for dmg metabolism, such as acetylator status... 

Individuals affected with porphyria present with acute attacks, skin lesions, or both. The onset of these attacks rarely occurs before puberty. An attack usually consists of severe abdominal pain and often neurological sequelae. During and after such attacks, excessive amounts of aminolevulinic acid and PBG are excreted in the urine. The most common porphyria is PBG deaminase deficiency (acute intermittent porphyria), which primarily affects liver function. A positive result coupled with a clinical indication of hepatosplenomegaly suggests that evaluation for tyrosine metabolites in the urine should be pursued (using the nitrosonaphthol test). 

In most porphyrias, excess metabolites can be detected in urine. Less polar porphyrins (i.e., coproporphyrins and protoporphyrin) are detectable in feces as they are excreted by the bile. The apolar protoporphyrin is eventually only detectable in blood. Porphyrins can easily be detected and measured by their intense fluorescence in mineral acids. The excitation wavelength is around 404 nm, and emission at about 615 nm. ALA is derivatized to a pyrrole and both, ALA and PBG, are detected by dimethylaminobenzaldehyde (DMAB), as described by Mauzerall and Granick [7]. 

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. 

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. 

Increased porphyrins in clear fluid such as urine may be detected directly by their pink fluorescence if exposed to long ultraviolet (Fig. 7.3.2). The specificity of this screening assay may be improved if porphyrins are extracted by talcum [8]. These isolated porphyrins may be quantified using a spectrofluorimeter. As different porphyrias show specific excretion patterns, separation of the main porphyrins is desirable. The formerly used fractionated extraction enabled to separate the uroporphyrin fraction from the coproporphyrin fraction. In addition to uroporphyrin, the first fraction includes heptacarboxy- and part of hexacarboxyporphyrins, and in addition to coproporphyrin, the second fraction includes part of hexacarboxy- and pentacar-boxyporphyrins. Later on, thin-layer chromatography of methylester derivatives is used. 

Fig. 7.3.3a-d Chromatogram of normal urine (a), urine from an individual with acute (in this case intermittent) hepatic porphyria (b), urine from an individual with porphyria cutanea tarda (c), and an undiluted sample from an individual with congenital erythropoietic porphyria (d). See typical pathological values for interpretation... 

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... 

One of the rarer porphyrias results in an accumulation of uroporphyrinogen I, an abnormal isomer of a protoporphyrin precursor. This compound stains the urine red, causes the teeth to fluoresce strongly in ultraviolet light, and makes the skin abnormally sensitive to sunlight. Many individuals with this porphyria... 

Urine from a patient with porphyria cutanea tarda (right) and from a patient with normal porphyrin excretion (left). 

The porphyrias. The human body does not use all of the porphobilinogen produced, and a small amount is normally excreted in the urine, principally as coproporpyrins (Fig. 16-5). In a number of hereditary and acquired conditions blood porphyrin levels are elevated and enhanced urinary excretion (porphy-... 

Inborn metabolic diseases that interfere with heme biosynthesis are called porphyrias. Porphyrias have a variety of symptoms. A deficiency in the enzyme responsible for the condensation of porphobilinogen to the 4-membered ring system leads to a condition called acute intermittent porphyria, which is characterized by occasional episodes of abdominal pain and psychiatric symptoms. Defects in the later enzymes of the pathway lead to an excess accumulation of the uroporphobilinogens in the tissues, where they cause a variety of symptoms, including hairy skin, skeletal abnormalities, light sensitivity, and red urine. Individuals with this disease are still anemic—a condition that can be alleviated somewhat by the heme acquired from drinking blood. This combination of traits sounds like the werewolf and vampire legends of Europe, which may have their base in this rare biochemical disease. 

It may be noted that although the human organism is capable of degrading metal-containing porphyrins such as heme, it has no means of degrading porphyrins containing no metal, for example coproporphyrins and uroporphyrins. These must be excreted as such. The latter two are water-soluble and are thus found in urine and to some extent in the feces. Protoporphyrins, however, are largely water-insoluble and are excreted in the feces. Finally, it may be mentioned that porphyrias make their appearance after puberty. This has been associated with the appearance of 5/3-steroid reductases, as discussed above. 

If coprophyrinogen III decarboxylase (oxidase) were defective in a porphyria patient, which compound would be least likely to be found in the feces or urine of the patient ... 

During an acute attack, a fresh urine sample which has been protected from light should be sent to a specialist laboratory to be tested for aminolaevulinic acid and porphobilinogen concentrations. If urinalysis confirms raised urinary excretion of aminolaevulinic acid and porphobilinogen, an analysis of faecal porphyrins can be used to identify the specific porphyria. In acute intermittent porphyria faecal porphyrin levels are generally normal. 

Ehrlich s aldehyde test can be used to confirm a diagnosis of acute intermittent porphyria. Equal volumes of urine and Ehrlich s reagent are mixed a pink colour indicates raised urinary concentration of either porphobilinogen or urobilinogen. In acute intermittent porphyria, raised porphobilinogen is present and the pink precipitate formed is insoluble in chloroform. 

Tab. 3.3 Reference values of porphyrins and their precursors in urine and the stool for differential diagnosis of porphyria...

The colourless porphyrinogens easily convert to coloured red-fluorescent uroporphyrins at 366 nm when there is a sufficient amount of oxygen. This causes a red colour in the urine, which becomes darker (burgundy red) when left in contact with air. The red-fluorescent specimen obtained by liver biopsy in chronic hepatic porphyria is impressive, (s. pp 145, 158) (s. fig. 7.10)... 

In cases of suspected hepatic porphyria, instant orientation is gained by examining the urine for evidence of 5-... 

Hepatic porphyrias show the following characteristics (1.) intermittent course, (2.) increased ALA synthase activity, and (3.) acute attacks induced or manifesting during the latency period due to numerous causes such as alcohol (281), hunger, carbohydrate deficiency, hormones, stress, intoxication, metabolic products and medicaments, (s. tab. 31.13) The diagnosis is based upon the clinical symptomatology and the excretion pattern of the porphyrins or their precursors in the urine and faeces as well as their concentrations in the erythrocytes and plasma, (s. tab. 31.14)... 

---