This testing information is provided for educational purposes only and is not intended to replace the independent medical judgment for any healthcare professional.
Consider ordering random (spot) urine tests to look for elevated levels of aminolevulinic acid (ALA), porphobilinogen (PBG), and porphyrins, the neurotoxins that are believed to cause attacks and disease manifestations.1-5
RANDOM (SPOT) URINE TESTS AND GENETIC TESTING1-6
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 can be toxic when elevated in patients with symptomatic AHP. PBG and ALA may remain elevated during recovery from an 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 help inform 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 generally 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
- It is not recommended to use urine porphyrins alone to diagnose AHP, as they can be elevated for several reasons7
The optimal time to test is during or shortly after an attack when ALA and PBG levels have spiked because levels may fall when symptoms resolve. While a random (spot) urine test is the most common method used to inform a diagnosis, a genetic test can also be performed to differentiate which AHP type a patient may have and can be useful for at-risk family screening.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 of AHP while PBG is elevated for only the 3 most common forms (excluding ADP), but both ALA and PBG levels may decrease between attacks7§
- It is recommended to normalize test results to urine creatine 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 typically be light-protected and frozen or refrigerated based on laboratory specifications. Short delays in refrigeration/freezing should not cause false negative results. For the most up-to-date testing and protocol information, please refer to your local laboratories for specific requirements and guidance3,10
- Once a diagnosis of AHP is 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 who 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 sponsors genetic testing and counseling.
The Alnylam Act® offers third-party genetic testing and counseling for patients who may have acute hepatic porphyria at no charge to patients, physicians, and payers.
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 certain other countries. Genetic counseling is 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 patients, healthcare professionals, or 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.