Investigations
1st investigations to order
plasma total porphyrins
Test
Sensitive and specific for porphyrias causing blistering skin lesions. When high, analysis by high-performance liquid chromatography (HPLC) is important to document PCT. Measurement is important to assess severity and to assess response to treatment.
Result
elevated (5 to 30 micrograms/dL)
plasma fluorescence emission
urinary total porphyrins
Test
Sensitive for PCT but lacks specificity because urine porphyrins are elevated in all but one type of porphyria, and more subject to non-specific elevations in other conditions.
When high, analysis by HPLC is important to document PCT.
Result
elevated (approximately 500 and 5000 micrograms/L [750 and 7500 nanomoles/L])
erythrocyte total porphyrins
Test
Normal or modestly elevated in PCT. Substantial elevation may indicate a concurrent marrow disorder (e.g., myelofibrosis).
Marked elevation in erythrocyte porphyrins suggests less common blistering porphyria, such as congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and homozygous forms of acute intermittent porphyria, hereditary coproporphyria (including a variant form termed harderoporphyria), and variegate porphyria; all of which can present as skin lesions that mimic PCT in children or adults.
Result
normal or moderately elevated
Investigations to consider
fractionation of plasma porphyrins by high-performance liquid chromatography (HPLC)
Test
If the total porphyrins are elevated, plasma porphyrins are fractionated by HPLC, showing a characteristic predominance of uroporphyrin and heptacarboxyl porphyrin.
Sensitive and specific if elevations are substantial and erythrocyte porphyrins are not markedly elevated.
Result
predominance of uroporphyrin and heptacarboxyl porphyrin
fractionation of urinary porphyrins by HPLC
Test
If the total porphyrins are elevated, urine porphyrins are fractionated by HPLC, showing a characteristic predominance of uroporphyrin and heptacarboxyl porphyrin.
Sensitive and specific if elevations are substantial and erythrocyte porphyrins are not markedly elevated.
Result
predominance of uroporphyrin and heptacarboxyl porphyrin
erythrocyte uroporphyrinogen decarboxylase (UROD) activity
Test
Sensitive for identifying patients with type 2 PCT with a UROD mutation, which is an inherited susceptibility factor.
Available from a few specialised laboratories.
Result
low (~50% of normal) if heterozygous UROD mutation
faecal porphyrins
Test
To help differentiate PCT from variegate porphyria (when plasma porphyrin spectral analysis is not available) and hereditary coproporphyria.
Result
normal or moderately increased, with increased isocoproporphyrins
DNA studies
Test
Sensitive to identify patients who are heterozygous for a UROD mutation, which is an inherited susceptibility factor, and to identify hereditary haemochromatosis gene (HFE) mutations.
Some PCT patients are homozygous or heterozygous for HFE gene mutations.
Result
UROD mutation; HFE mutations
Liver function tests
Test
Liver function abnormalities are common but are usually mild.
Serum levels of alanine amino transferase, aspartate amino transferase, alkaline phosphatase, gamma glutamyl transferase, and total, direct, and indirect bilirubin may be elevated.
Result
abnormal
serum ferritin
Test
Serum ferritin is measured to assess for iron overload and may be increased in patients with iron overload and in liver disease (acute phase response). It is a useful target for therapeutic phlebotomy.
Some patients with HFE mutations may have iron overload.
Result
elevated in iron overload
liver biopsy
Test
Patients with iron overload (e.g., serum ferritin >1000 nanograms/mL), with abnormal liver enzymes or associated hepatitis C should be considered for liver biopsy. PCT is not a specific indication for liver biopsy, so the usual indications for liver biopsy apply.
Result
porphyrin-containing inclusions within hepatocytes and non-specific histological abnormalities; elevated iron content in iron overload
skin biopsy
Test
Skin biopsy will show features of subepidermal blister formation, but this is seen in other blistering porphyrias and is not by itself diagnostic.[15]
Result
features of subepidermal blister formation
serum HIV enzyme-linked immunosorbent assay
Test
Management of PCT includes identification and management of susceptibility risk factors, one of which is HIV infection.
Further HIV confirmatory tests (serum p24 antigen, serum Western blot, or serum HIV DNA PCR) should be performed.
Result
positive in patients with HIV infection
serum hepatitis C surface antibodies
Test
Management of PCT includes identification and management of susceptibility risk factors, one of which is hepatitis C.
Confirmation of active hepatitis C infection should be done using PCR, branched-chain DNA analysis, or transcription-mediated amplification.
Result
positive in patients with hepatitis C infection
creatinine
Test
Management of PCT includes identification and management of susceptibility risk factors, one of which is end-stage renal disease.
Result
elevated in patients with end-stage renal disease
urea
Test
Management of PCT includes identification and management of susceptibility risk factors, one of which is end-stage renal disease.
Result
elevated in patients with end-stage renal disease
haematocrit
Test
Monitored during repeated phlebotomies.
Anaemia in a patient with PCT suggests a concurrent condition causing anaemia (e.g., myelofibrosis).
Result
normal; low if anaemic
haemoglobin
Test
Monitored during repeated phlebotomies.
Anaemia in a patient with PCT suggests a concurrent condition causing anaemia (e.g., myelofibrosis).
Result
normal; low if anaemic
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