Investigations
1st investigations to order
urinary porphobilinogen (PBG) and total porphyrins
Test
Substantial elevation of PBG can be confirmed in a single-void urine specimen. This is the most useful single screening test for acute porphyrias, with high sensitivity and specificity during or soon after acute attacks.[16]
PBG elevation, if substantial, confirms that a patient has AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP), but not that current symptoms are due to porphyria. PBG elevation persists between attacks in many patients with AIP (less often in HCP and VP), so diagnosis of an attack is clinical.
Results may be reported initially per litre, but final results should be normalised to creatinine and, if abnormal, followed by second-line testing.
should be confirmed by later measurement of delta-aminolevulinic acid (ALA) and PBG and total porphyrins in the same sample.
Result
for PBG: upper limits of normal (ULN) vary more than 10-fold between laboratories related to different methods of measurement - therefore, results should be interpreted based on actual values rather than fold increases above a ULN; to support a diagnosis of AIP, HCP, or VP, levels should greatly exceed 5 mg/g creatinine (2.5 mmol/mol creatinine); total urine porphyrin excretion is expected to greatly exceed 300 nmol/g creatinine or 200 ug/g creatinine (52 nmol/mmol creatinine) in active porphyrias, but is non-specific and second-line testing is needed to determine if this finding can be attributed to porphyria
serum PBG
Test
Quantitative measurement of serum PBG is an initial test ordered in patients with advanced renal disease and suspected AIP.
It is less sensitive than urinary PBG in patients with normal renal function.
Result
elevated, but expected range not established
Investigations to consider
delta-aminolevulinic acid (ALA)
Test
Quantitative assessment in a single-void specimen, with result normalised to creatinine.
Less sensitive than urinary PBG for first-line screening.
Result
increased along with PBG in AIP, hereditary coproporphyria, and variegate porphyria, but usually less than PBG (when expressed in mg/g creatinine); to support a diagnosis of acute porphyria, levels are expected to exceed 10 mg/g creatinine (6.9 mmol/mol creatinine); upper limits of normal vary greatly between laboratories, so absolute values rather than fold increases should be noted; ALA and porphyrins, but not PBG, are increased in other conditions, including lead poisoning, hereditary tyrosinaemia, and ALA dehydratase porphyria
plasma total porphyrins (including plasma fluorescence scanning)
Test
Part of second-line testing to differentiate AIP and hereditary coproporphyria (HCP) from variegate porphyria (VP).
Result
normal or slightly increased in AIP and most cases of HCP; increased with a diagnostic fluorescence peak in VP when plasma is diluted at neutral pH
urinary porphyrins using high-performance liquid chromatography (HPLC)
Test
Fractionation of urine porphyrins is not helpful for differentiation of AIP from hereditary coproporphyria (HCP) and variegate porphyria (VP).
Result
urinary total porphyrins increased during attacks and often between attacks in all acute porphyrias, but the pattern of individual porphyrins does not reliably differentiate AIP, HCP, and VP
faecal total porphyrins (if elevated, fractionation of individual porphyrins by HPLC)
Test
Part of second-line testing to differentiate AIP from hereditary coproporphyria and variegate porphyria, in which faecal porphyrins are substantially increased.
Result
normal or slightly increased in AIP; markedly increased in active hereditary coproporphyria with a predominance of coproporphyrin III, and in variegate porphyria with a predominance of coproporphyrin III and protoporphyrin
faecal porphyrins using HPLC
Test
Faecal coproporphyrin analysis is diagnostically helpful in acute porphyrias and particularly helps to differentiate active AIP from hereditary coproporphyria (HCP) and variegate porphyria (VP).[17][18]
Result
faecal total porphyrins are normal or slightly elevated in AIP, but markedly elevated in active HCP and VP; coproporphyrin III is markedly elevated and is the predominant faecal porphyrin in active HCP, and coproporphyrin III and protoporphyrin are both markedly elevated in active VP; the coproporphyrin III/I ratio is elevated in all acute porphyrias (AIP, HCP, and VP), and this ratio may be elevated in latent HCP and VP even when total faecal porphyrins are normal
erythrocyte porphobilinogen deaminase activity
Test
Helps in confirming a diagnosis of AIP and in differentiating AIP from other acute porphyrias.
Also useful in identifying carriers of an AIP trait in families where the index case has demonstrated AIP and decreased enzyme activity.[8][19]
Result
reduced by approximately 50% in most patients with AIP; however, there is overlap between the ranges for AIP and normals, in part because enzyme activity is related to erythrocyte age and affected by red cell perturbations
porphobilinogen deaminase/hydroxymethylbilane synthase gene sequencing
Test
Helps to confirm a diagnosis of AIP.[16] Effective for finding family members with latent AIP when the familial mutation is known.
Sequencing may not detect some cryptic mutations and complete or large deletions.
Result
identifies a known pathogenic mutation or an unknown mutation that may likely be pathogenic, a variant of unknown significance, or a known benign variant
serum sodium levels
Test
Hyponatraemia may be present due to the syndrome of inappropriate ADH secretion reflecting hypothalamic involvement.
Result
below the reference range
CT or MRI brain
Test
Reversible CT or MRI changes that resemble the changes of the posterior reversible encephalopathy syndrome may accompany an acute attack with neuropsychiatric manifestations.
Result
may be abnormal during acute attacks
Use of this content is subject to our disclaimer