Frequently asked questions (FAQ) on acute hepatic porphyria diagnosis
Here are the frequently asked questions (and their answers) about acute hepatic porphyria diagnosis.
1. If symptomatic, is a random urine sample appropriate for PBG and ALA testing or does it need to be a 24-hour sample?
Urinary PBG and ALA are best analysed in a fresh, random sample collected without any preservative. The sample should be then protected from light (e.g. container wrapped in aluminium foil).
A 24-hour urine collection is not recommended because it is cumbersome to obtain a complete 24 hours sample, it can delay diagnosis and it can underestimate the PBG concentration.
2. Do blood, urine and stool samples have to be taken in the dark and with the bottles and tubes completely covered, or is it best practice to simply cover immediately afterwards?
The samples (blood, urine and stool) are collected under normal lighting conditions.
But it is important that immediately after collection, the containers with the samples are protected from light (opaque container or wrapped in aluminium foil).
Data indicate that PBG is stable in urine in the dark for up to 48 hours when refrigerated and for at least a month when frozen. However, repeated freeze cycles are not recommended.
Acute attacks are always accompanied by highly increased excretion of PBG and ALA in the urine. This is the case for acute attacks occurring in AIP, HCP or VP patients.
It is important that the results are interpreted by a porphyria expert healthcare professional.
No, they cannot. From an analytical point of view, IV glucose or carbohydrate loading are not known as interfering molecules and thus do not cause a false negative urinary PBG/ALA test.
In some situations, when e.g. a patient receives infusion of fluids, the urine may be highly diluted and thus unsuitable for analysis. Therefore, it is important that the results are reviewed by a porphyria expert healthcare professional, who will take into account the degree of dilution when interpreting the results, and if necessary, may request a new urine sample.
6. Is an enzyme test necessary for accurate diagnosis of an acute porphyria? When would it be needed?
No, an enzyme test is not mandatory for accurate diagnosis.
The diagnosis of an acute attack is based on demonstrating increased PBG excretion in urine. As soon as a diagnosis of acute porphyria has been established, it is essential to identify the type of acute porphyria in order to provide appropriate advice for the patient and their family. This is done by the analysis of urinary, faecal and plasma porphyrins of the overt patient.
Enzyme measurements are not required for the diagnosis and may mislead due to overlap between normal and disease ranges.
The demonstration of a disease-specific mutation in the appropriate gene identifies a genetic trait for porphyria, but, by itself, gives no indication of disease activity.
Once the genetic analysis identifying the causative mutation in the appropriate gene has been performed for the affected family member, family screening could be organised in collaboration with a clinical genetics service to ensure appropriate counselling and sample collection.
7. Is the testing process for acute symptomatic children (under 15) the same as for acute symptomatic adults? If it is different, is it possible to explain the difference.
The testing process for acute symptomatic children is the same as for acute symptomatic adults.
The diagnosis of an acute attack of porphyria in children, requires the analysis of PBG and ALA in urine, sampled when in the symptomatic phase.
Of note, acute attacks are very rare before puberty.