The Challenges Of Testing For And Diagnosing Porphyrias

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attacks rarely occur before puberty, and attack frequency and severity decline after menopause. Interestingly, a subset of female patients experience regular, cyclical, exacerbations of disease in conjunction with menses. A variety of drugs, including alcohol, have been implicated in the induction of acute porphyric attacks. There is consensus regarding the use and safety of many common medications in patients with AIP. Other drugs are not as well understood. Some commonly used drugs, which have been classified as safe or unsafe for use by patients with an acute porphyria, are listed in Table 1. More extensive lists, including drugs whose safety is still in question, are available elsewhere. 3 Medications previously established as safe should be used whenever possible in patients with asymptomatic or symptomatic AIP. Nutritional status, in particular decreased caloric intake, has been shown to induce the onset of an acute attack. Intercurrent illnesses and surgery exhibit a causal relationship, possibly due to increased energy requirements during these times. Additionally, psychological stress has been reported to contribute to AIP symptomology, though the underlying mechanisms are not understood. Precipitating factors likely act in an additive fashion, and the trigger(s) of a particular crisis, cannot always be ascertained. Table 1. Medications and the acute porphyrias Treatment for Acute Porphyrias Hospitalization is often necessary for the treatment of acute attacks. Crises are treated with increased carbohydrate intake that may occur via intravenous administration. Heme (hematin or heme arginate) therapy allows for the excretion of ALA and PBG. Efficacy is compromised if heme therapy is delayed, so treatment should commence as soon as possible after the onset of a crisis. Symptomatic treatment includes frequent doses of analgesics to control pain, and phenothiazines may be administered to control nausea, vomiting, and anxiety. Given that pain tends to be severe, narcotics are typically the analgesia of choice, as nonnarcotic agents are usually inadequate. Treatment for asymptomatic patients or between acute porphyria crises largely relies upon the prevention of potentially life-threatening episodes. At-risk individuals should be counseled to avoid medications known to precipitate attacks (Table 1), to avoid excessive alcohol intake, to seek prompt treatment for other intercurrent illnesses, and to maintain proper nutritional status, including the avoidance of crash dieting. Patients should be encouraged to wear a medical alert bracelet allowing for proper management in the event that the patient becomes temporarily incapacitated as a result of an accident or acute crisis. Photosensitivity can be minimized in VP and HCP patients by avoidance of sun exposure, protective clothing, and pharmacotherapy in the form of a beta-carotene analog, canthaxanthine. Testing for Porphyria By following our suggested testing strategy, the quality of patient care and cost-effectiveness of testing can be maximized. Depending upon the specific type of porphyria suspected, certain tests are more informative than other assays. In general, a 24-hour urine porphyrins (#8562 Porphyrins, Quantitative, Urine) analysis that includes porphobilinogen is the most effective screening tool. However, when EPP is the potential diagnosis, an erythrocyte porphyrin (#8536 Porphyrins, Total, Erythrocytes and #8735 Porphyrins, Fractionation, Erythrocytes) and protoporphyrin fractionation (#8739 Protoporphyrins, Fractionation, Erythrocytes) are the most appropriate tests to perform. For a listing of informative biochemical findings for each type of porphyria, please refer to Table 2. Testing strategies for each suspected porphyria are outlined in Table 3, page 10. Ordering a battery of tests does not enhance the quality of patient care. Rather, a stepwise diagnostic approach is the most effective means of ruling in/out a specific porphyria. In most cases, when the result of the urine porphyrins test is normal, subsequent testing in the form of fecal, plasma, and erythrocyte porphyrin analyses and enzyme assay are not recommended. As shown, the 24-hour urine porphyrins (#8562 Porphyrins, Quantitative, Urine) analysis is the most appropriate starting point. If a 8 11/02
Table 2. Informative Biochemical Findings in Porphyria particular diagnosis is suspected, additional first-line testing may be appropriate (tests listed in black in Table 3, page 10); other analyses (listed in red) may be delayed until initial results are available. While providing minimal clinical value, additional testing creates unnecessary expense to the referring laboratory or physician, health insurance company, and patient. For at least 1 week prior to testing for porphyria, and under the guidance of the physician, the use of medications should be avoided or minimized. If clinically inadvisable, or if the patient is in a crisis, a list of medications should accompany the specimen. Additionally, the patient should abstain from alcohol consumption for at least 24 hours prior to specimen collection. Abnormal results are reported with a detailed interpretation including an overview of the results and their significance, a correlation to available clinical information provided with the specimen, differential diagnosis, and recommendations for additional testing when indicated and available. For consultation regarding porphyrias, please contact a laboratory director or genetic counselor in the Biochemical Genetics Laboratory by calling Mayo Lab Inquiry (1-800-533-1710). Continues on page 10. References 1. De Siervi A, Rossetti MV, Parera VE, Mendez M, Varela LS, del C Batlle AM. Acute intermittent porphyria: biochemical and clinical analysis in the Argentinean population. Clin Chim Acta 1999 Oct;288(1-2):63-71 2. Andersson C, Floderus Y, Wikberg A, Lithner F. The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study. Scand J Clin Lab Invest 2000 Nov;60(7):643-83 3. Anderson KE, Sassa S, Bishop DF, Desnick RJ: Disorders of Heme Biosynthesis: X-Linked Sideroblastic Anemia and the Porphyrias (Chapter 124). In The Metabolic & Molecular Bases Of Inherited Disease, 8th edition. Edited by CR Scriver. New York, McGraw-Hill, 2001, pp 2991-3062 4. Matter, SET and Tefferi, A. Acute Porphyria: The Cost of Suspicion. Am J Med 1999 Dec;107:621-623 11/02 9
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The Challenges Of Testing For And Diagnosing Porphyrias

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