To confirm if a patient has AHP, order a random (spot) urine test for elevated levels of aminolevulinic acid (ALA), porphobilinogen (PBG), and porphyrins, the toxins that are believed to cause disease manifestations.1-6
Confirm the diagnosis of AHP with a random (spot) urine test1-6
AHP=acute hepatic porphyria; ALA=aminolevulinic acid; PBG=porphobilinogen.
*PBG and ALA occur naturally in the heme biosynthesis pathway in the liver but can be toxic when elevated in patients with symptomatic AHP. PBG and ALA may remain elevated during recovery from an AIP or other type of AHP attack.2,5,8
†Urine porphyrins can help differentiate between types of AHP.3
The PBG random (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.1,5
Testing for AHP: CPT Codes and Laboratory Values1, 5, 9
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 type (AIP, HCP, VP, or ADP).
- Specimen requirements are lab-specific
- During acute episodes, PBG is typically markedly elevated (>10-fold ULN) in AIP7
- Urine porphyrins are nonspecific and should not be used alone to diagnose AHP7
Samples should be collected during symptomatic periods because levels may fall when symptoms resolve. While a random (spot) urine test is key to confirming a diagnosis, a genetic test can also be performed to differentiate which type of AHP 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 levels7
- ALA levels are elevated during symptomatic periods for all 4 types while PBG is elevated for only the 3 most common forms (excluding ADP), but these levels may decrease between attacks7§
- Normalize test results to urine creatinine to avoid false negatives, especially in diluted 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 test4,6
- 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 type of AHP. 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 toxic levels of ALA and PBG3
§ALA and PBG are porphyrin precursors that occur naturally in the heme biosynthesis pathway in the liver but reach toxic levels in patients with a symptomatic AHP.2,5
One Genetic Testing Option
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 created to provide access to genetic testing and counseling to patients as a way to help people make more informed decisions about their health.
- While Alnylam provides financial support for this program, 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 uses healthcare professional contact information for research and commercial purposes
- Genetic testing is available in the US and Canada. Genetic counseling is only available in the US
- Healthcare professionals or patients who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Alnylam product
- No payers, including government payers, are billed for this program
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. Ramanujam VM, Anderson KE. Curr Protoc Hum Genet. 2016; 86:17.20.1-17.20.26. 7. Bissell DM, Wang B. J Clin Transl Hepatol. 2015;3(1):17-26. 8. Gouya L, Bloomer JR, Balwani M, et al. Presented at: 2017 International Congress on Porphyrins and Porphyrias; June 26, 2017; Bordeaux, France. 9. Whatley SD, Mason NG, Woolf JR, Newcombe RG, Elder GH, Badminton MN. Clin Chem. 2009;55(7):1406-1414. 10. Woolf J, Marsden JT, Degg T, et al. Ann Clin Biochem. 2017;54(2):188-198.