Diagnostic testing for active porphyrias

Concurrent or recent clinical manifestations	Initial testing	Additional testing (if initial results are positive)	Types of porphyria identified	Enzyme and DNA tests
Acute neurovisceral	Spot urine PBG and total porphyrins (normalized with urine creatinine)	Spot urine ALA, PBG, and total porphyrins (quantitative, normalized with urine creatinine) Plasma porphyrins* Erythrocyte porphyrins^¶ Fecal porphyrins	Delta-aminolevulinic acid dehydratase porphyria (ADP)	Erythrocyte ALAD Sequence ALAD gene
			Acute intermittent porphyria (AIP)	Erythrocyte PBGD Sequence PBGD gene
			Hereditary coproporphyria (HCP)	Sequence CPOX gene
			Variegate porphyria (VP)	Sequence PPOX gene
Blistering photosensitivity	Total porphyrins (plasma*, serum, or spot urine), with fractionation if elevated	Erythrocyte total porphyrins Urinary ALA and PBG Fecal total porphyrins	Porphyria cutanea tarda (PCT)	Erythrocyte UROD Sequence UROD gene^Δ
			Hepatoerythropoietic porphyria (HEP)	Erythrocyte UROD Sequence UROD gene
			HCP	Sequence CPOX gene
			VP	Sequence PPOX gene
			Congenital erythropoietic porphyria (CEP)	Erythrocyte UROS Sequence UROS gene
Nonblistering photosensitivity	Total erythrocyte porphyrins^¶	Erythrocyte metal-free and zinc protoporphyrin; plasma total porphyrins and fluorescence scan	Erythropoietic protoporphyria (EPP)	Sequence FECH gene
Nonblistering photosensitivity	Total erythrocyte porphyrins^¶		X-linked protoporphyria (XLP)	Sequence ALAS2 gene

First-line testing for symptomatic patients is guided by clinical features (ie, neurovisceral, cutaneous chronic blistering, or cutaneous acute nonblistering). All spot urine measurements should be normalized with spot urine creatinine. If initial testing is positive, further comprehensive testing follows to identify the type of acute porphyria. Enzyme measurements may be used but are not available for all porphyrias. DNA testing usually follows establishment of a biochemical diagnosis. Refer to UpToDate topics on overview of porphyria and specific porphyrias for additional details and testing in asymptomatic patients.

PBG: porphobilinogen; ALA: delta-aminolevulinic acid; ADP: delta-aminolevulinic acid dehydratase porphyria; ALAD: delta-aminolevulinic acid dehydratase; PBGD: porphobilinogen deaminase; CPOX: coproporphyrinogen oxidase; PPOX: protoporphyrin oxidase; UROD: uroporphyrinogen decarboxylase; UROS: uroporphyrinogen III synthase; FECH: ferrochelatase; ALAS2: delta-aminolevulinate synthase-2.
* Plasma porphyrins should include measurement of the total, fractionation if the total is elevated, and determination of the fluorescence peak wavelength at neutral pH.
¶ It is important to verify that the method used by the laboratory measures all erythrocyte porphyrins and not just zinc protoporphyrin.
ΔUROD mutations are neither required nor specific for a diagnosis of PCT. UROD mutations are found in approximately 20% of patients with PCT and therefore are helpful if present. The presence of a UROD mutation is a predisposing factor but not sufficient to cause PCT.

Graphic 89036 Version 12.0

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Diagnostic testing for active porphyrias