Take a closer look at simplifying the diagnostic path
To confirm if a patient has AHP, order spot urine tests for elevated levels of aminolevulinic acid (ALA), porphobilinogen (PBG), and porphyrins, the neurotoxins that are believed to cause disease manifestations.1-5
Confirm the diagnosis of AHP with spot urine tests1-5
AHP=acute hepatic porphyria; ALA=aminolevulinic acid; PBG=porphobilinogen.
*PBG and ALA are neurotoxic intermediates that occur naturally in the heme biosynthesis pathway in the liver but reach neurotoxic levels in patients with symptomatic AHP. PBG and ALA may remain elevated during recovery from an AIP or other type of AHP exacerbation.2,5,7
†Urine porphyrins can help differentiate between AHP subtypes.3
The PBG spot urine test is highly specific and can confirm a diagnosis of AHP, while the ALA test is helpful for differential diagnosis and confirmation of ADP subtype.1,5
Testing for AHP: CPT Codes and Laboratory Values1, 5, 8
Random Spot Urine Test
Laboratory Values by Acute Hepatic Porphyria (AHPs) Subtype
Delta-Aminolevulinic Acid (ALA)
‡Tests are more accurate when normalized per gram of urine creatinine and when sample is collected during acute episodes. 24-hour urine collection is not required. Additional testing (genetic or biochemical) may be required to differentiate AHP subtype (AIP, HCP, VP, or ADP).
- Specimen requirements are lab-specific
- During acute episodes, PBG is typically markedly elevated (>10-fold ULN) in AIP6
- Urine porphyrins are nonspecific and should not be used alone to diagnose AHP6
Samples should be collected during symptomatic periods because levels may fall when symptoms resolve. While spot urine tests are the key diagnostic tests to confirm a diagnosis, a genetic test can also be performed to differentiate which AHP subtype a patient may have.1,3,4
When Testing for AHP, Also Consider the Following:
- Ordering lab tests for urine porphyrins does not include assessment of ALA/PBG or their corresponding levels6
- ALA levels are elevated during symptomatic periods for all 4 subtypes while PBG is elevated for only the 3 most common forms (excluding ADP), but these levels may decrease between exacerbations6§
- Normalize test results to urine creatinine to avoid false negatives, especially in dilute urine samples3
- Urine color is normal, but can turn dark red or purple when exposed to a particular wavelength of light in a spectrum emission test4,9
- Samples should be refrigerated, frozen, and/or shielded from light, although short delays should not cause false negative results3,10
- Once a diagnosis of AHP is biochemically confirmed, gene sequencing can be used to identify the mutation and the AHP subtype. Consider genetic testing of family members of patients diagnosed with AHP to identify individuals that may also carry an AHP gene mutation and potentially have elevated neurotoxic levels of ALA and PBG3
- There are no approved therapies to prevent exacerbations or treat chronic symptoms
§ALA and PBG are porphyrin precursors that occur naturally in the heme biosynthesis pathway in the liver but reach neurotoxic levels in patients with a symptomatic AHP.2,5
Alnylam Pharmaceuticals sponsors no-charge, third-party genetic testing and counseling for individuals who may carry gene mutations known to be associated with AHP.
The Alnylam Act® program was developed to reduce barriers to genetic testing and counseling to help people make more informed decisions about their health. While Alnylam provides financial support for this program, all tests and services are performed by independent third parties. Healthcare professionals must confirm that patients meet certain criteria to use the program. Alnylam receives de-identified patient data from this program, but at no time does Alnylam receive patient identifiable information. Alnylam receives contact information for healthcare professionals who use this program. Genetic testing is available in the US and Canada. Genetic counseling is only available in the US. Healthcare professionals who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Alnylam product.Discover Alnylam Act®
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References: 1. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Ann lntem Med. 2005;142(6):439-450. 2. Bissell DM, Anderson KE, Bonkovsky HL. N Engl J Med. 2017;377(9):862-872. 3. Balwani M, Wang B, Anderson KE, et al; for the Porphyrias Consortium of Rare Diseases Clinical Research Network. Hepatology. 2017;66(4):1314-1322. 4. Ventura P, Cappellini MD, Biolcati G, Guida CC, Rocchi E; Gruppo Italiano Porfiria (GrlP). Eur J Intern Med. 25(6):497-505. 5. Pischik E, Kauppinen R. Appl Clin Genet. 2015;8:201-214. 6. Bissell DM, Wang B. J Clin Transl Hepatol. 2015;3(1):17-26. 7. Gouya L, Bloomer JR, Balwani M, et al. Presented at: 2017 International Congress on Porphyrins and Porphyrias; June 26, 2017; Bordeaux, France. 8. Whatley SD, Mason NG, Woolf JR, Newcombe RG, Elder GH, Badminton MN. Clin Chem. 2009;55(7):1406-1414 9. Ramanujam VM, Anderson KE. Curr Protoc Hum Genet. 2016; 86:17.20.1-17.20.26. 10. Woolf J, Marsden JT, Degg T, et al. Ann Clin Biochem. 2017;54(2):188-198.