The Porphyrias Consortium

Information for Patients and Families

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Information for Professionals:

Acute Hepatic Porphyrias:

Acute Intermittent Porphyria

Hereditary Coproporphyria

Variegate Porphyria

Aminolevulinate-dehydratase Deficiency
Porphyria

Cutaneous Porphyrias:

Porphyria Cutanea Tarda

Hepatoerythropoietic Porphyria

Congenital Erythropoietic Porphyria

Erythropoietic Protoporphyria and X-Linked Protoporphyria

Diagnosis of the Porphyrias

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First-line Testing:

The porphyrias may cause problems with the nervous system, the skin, or both. Many carriers of a porphyria gene have no symptoms. Acute porphyrias may lead to a variety of effects on the nervous systems such as abdominal pain, nausea, vomiting, pain in the extremities and elsewhere, muscle weakness and altered mental functioning. Cutaneous porphyrias lead to skin manifestations in sun-exposed areas (photosensitivity). These may include chronic blistering or sudden pain and swelling. Some porphyrias have both cutaneous and neurological manifestations.s

Symptoms	Most sensitive and specific test for screening when symptoms are present
Table 1. First-line testing for patients in whom porphyria is suspected as a cause of either neurological symptoms or photosensitivity.
Neurological (acute abdominal pain, etc.)	Urinary delta-aminolevulinic acid and porphobilinogen (a total urinary porphyrin determination is also recommended.)
Skin photosensitivity	Total plasma porphyrins

Acute porphyrias

When an acute porphyria is suspected due to neurological symptoms such as abdominal pain, the first-line screening test is measurement of porphobilinogen (PBG) in urine. PBG is markedly increased in almost all patients with symptoms of acute porphyria and is never markedly increased in diseases other than acute Porphyria. Therefore this test is both sensitive and specific.

Measurement of PBG is often combined with delta-aminolevulinic acid (ALA) and total urine porphyrins. ALA is increased, but PBG is not, in ALAD Porphyria (ADP), the most rare form of acute Porphyria. In some patients with acute Porphyria, urinary porphyrins may remain increased longer than ALA and PBG. But it must be remembered that increases in urinary porphyrins occur in other medical conditions, and are therefore much less specific than increases in ALA and PBG. In urgent situations, PBG can be measured immediately (as a STAT test) and the urine sample saved for later measurement of ALA and total porphyrins.

If urine ALA, PBG and total porphyrins are normal, it is quite certain that any recent symptoms are not due to an acute Porphyria. If these are markedly increased, further testing is needed. A minor (less than 2-fold) elevation in urine porphyrins (especially coproporphyrin) with normal ALA and PBG is nonspecific and may not require further testing.

Porphyria Type	HMB-synthase activity in red blood cells	Urine PBG	Urine ALA	Urine porphyrins	Fecal porphyrins	Plasma porphyrins
Table 2. Second-line testing for acute porphyrias: Laboratory findings that can differentiate between AIP, HCP and VP.
AIP	Decreased ~50% in 90% of cases	elevated	elevated	Markedly increased; mostly uroporphyrin	Normal or slightly increased	Normal or slightly increased
HCP	normal	elevated	elevated	Markedly increased; mostly coproporphyrin	Markedly increased; mostly coproporphyrin	Normal or slightly increased
VP	normal	elevated	elevated	Markedly increased; mostly coproporphyrin	Markedly increased; mostly protoporphyrin	Markedly increased; Fluorescence peak (at neutral pH) at ~626nm
ADP	normal	normal	elevated	Markedly increased; mostly coproporphyrin	Normal or slightly increased	Normal or slightly increased

Cutaneous porphyrias.

When a cutaneous porphyria is suspected due to skin photosensitivity, the first-line screening test should be measurement of total plasma porphyrins; the level can be expected to be very much increased in any patient with skin manifestations due to Porphyria. Plasma porphyrins are seldom increased in other medical conditions.

If this test is normal, cutaneous porphyrias that cause blistering skin lesions are effectively excluded. Further testing is needed if total plasma porphyrins are increased. However, although this is a highly effective screening test, it is less sensitive than an erythrocyte protoporphyrin determination in detecting EPP.

Porphyrin Type	Urine ALA / PBG	Urine porphyrins	Fecal porphyrins	Erythrocyte porphyrins	Plasma fluorescence emission peak
Table 3. Second-line testing for cutaneous porphyrias: Laboratory findings that can differentiate between CEP, PCT, EPP, XLP
CEP	normal	Increased; mostly uro- and coproporphyrin	Increased; mostly coproporphyrin	Increased; mostly Zn-proto-, copro-, and uroporphyrin	615-620nm
PCT & HEP	normal	Increased; mostly uro- and heptacarboxylate porphyrin	Increased; mostly isocopro-- and heptacarboxylate porphyrin	normal	615-620nm
EPP	normal	normal	Increased; mostly protoporphyrin	Increased; mostly protoporphyrin; free-proto significantly greater than Zn-protoporphyrin	626-634nm
XLP	normal	normal	Increased; mostly protoporphyrin	Increased; mostly protoporphyrin; free-proto equal to Zn-protoporphyrin	626-634nm