Porphyrias

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Porphyrias Testing Algorithm

Clinical Background

Porphyrias are inherited or acquired enzyme disorders of the heme biosynthetic pathway.

Clinical features of the two most common porphyrias (acute intermittent porphyria, porphyria cutanea tarda)

Acute intermittent porphyria (AIP)
- Neurologic, abdominal signs and symptoms
- Gender - predominantly females
- Average age of onset - 20-30 years
Porphyria cutanea tarda (PCT)
- Cutaneous signs and symptoms
- Gender - predominantly males
- Average age of onset - males 40-50 years

Categories of Porphyria

Acute - aminolevulinic acid dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP)
Nonacute - congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), erythropoietic protoporphyria (EPP)

Risk Factors

Genetics - transmitted as autosomal dominant disorders predominantly
PCT - associated with alcoholism, hepatitis C, hemochromatosis and autoimmune disorders

Pathophysiology

Heterogenous group of inherited disorders of heme synthesis
- A partial deficiency of one of seven enzymes in the pathway causes the clinical features of porphyria
- Defined by accumulation and excretion of heme precursors specific for the individual disease
Acute intermittent porphyria (AIP)
- Accumulation of smaller-size analytes early in the pathway
Porphyria cutanea tarda (PCT)
- Accumulation of larger-size analytes later in the pathway

Refer to Porphyrias topic at www.arupconsult.com for the diagram of Heme Biosynthetic Pathway

Clinical Presentation

Acute
- Neurologic symptoms
  - Muscular weakness and pain (proximal myopathy of the arms is common)
  - Mild sensory neuropathy (bathing trunk distribution), paresthesias
  - Psychiatric symptoms - confusion, hallucinations, psychosis
- Abdominal symptoms - abdominal pain (may be colicky or mimic acute abdomen), nausea, emesis, marked constipation, dark brown or red urine
- Precipitating factors
  - Drugs - anticoagulants, barbiturates, estrogen, ethanol, fasting, nicotine, sulfonamides
  - Diminished caloric intake
  - Infections
  - Surgery
Nonacute
- Cutaneous symptoms - bullous lesions on sun-exposed skin
- Precipitating factors - drugs (eg, ethanol, estrogens), iron

See Also

Hepatocellular Carcinoma

Immunobullous Skin Diseases Screening

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Porphyrias Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Porphobilinogen (PBG), Urine

ARUP #: 0080260

Methodology: Ion Exchange Chromatography/Spectrophotometry

Use:

Rule out acute intermittent porphyria (AIP) or other acute attack types of porphyrias associated with neurologic and/or psychiatric symptoms

Limitations:

24-hour specimen is more sensitive

Follow-up:

If test is negative, but high clinical suspicion still exists, repeat when symptoms are present

Test name: Aminolevulinic Acid (ALA), Urine

ARUP #: 0080103

Methodology: Ion Exchange Chromatography/Spectrophotometry

Use:

Evaluate suspected presence of ALA dehydratase deficiency porphyria, other acute porphyrias, lead poisoning and hereditary tyrosinemia

(PBG synthase testing)

Limitations:

24-hour specimen is more sensitive

Follow-up:

If lead poisoning is a possibility, order whole blood lead testing

Test name: Porphobilinogen (PBG) Deaminase, Erythrocyte

ARUP #: 0099550

Methodology: Enzymatic/Fluorometry

Use:

Useful in family studies to determine which members are at most risk for AIP

More correctly termed Hydroxymethylbilane synthase

Limitations:

Best performed in association with a specimen from an unaffected family member

Not recommended for diagnosis of an individual patient

Test name: Porphyrins, Urine

ARUP #: 0080460

Methodology: High Performance Liquid Chromatography

Use:

Evaluate cutaneous photosensitivity to exclude or rule out porphyria cutanea tarda (PCT)

Limitations:

24-hour specimen is more sensitive

Follow-up:

If test is negative, but high clinical suspicion still exists, repeat when symptoms are present

Test name: Porphyrins & Porphobilinogen (PBG), Urine

ARUP #: 0080305

Methodology: High Performance Liquid Chromatography/Ion Exchange Chromatography/Spectrophotometry

Use:

Evaluate patients with suspected porphyria presenting with neurologic and psychiatric symptoms

Limitations:

24-hour specimen is more sensitive

Test name: Porphyrins, Fecal

ARUP #: 0099824

Methodology: High Performance Liquid Chromatography

Use:

Distinguish among AIP, HCP, VP

Monitor EPP, HCP, VP

Limitations:

Bacterial modification of fecal porphyrins is extensive

Meat in diet may influence test results

Test name: Porphyrins, Serum Total

ARUP #: 0080429

Methodology: Scanning Fluorometry

Use:

Monitor PCT

Confirm VP

Limitations:

Does not differentiate specific porphyrin that is present

Test name: Zinc Protoporphyrin (ZPP), Whole Blood

ARUP #: 0020605

Methodology: Hematofluorometry

Use:

Screening test for EPP

Limitations:

Also elevated in early and late iron deficiency, anemia of chronic disease and chronic lead poisoning

Less specific than EP test

Follow-up:

To evaluate for lead poisoning, order whole blood lead testing

If ZPP is elevated order EP and/or serum porphyrins

Test name: Erythrocyte Porphyrin (EP), Whole Blood

ARUP #: 0020610

Methodology: Extraction/Fluorometry

Use:

Evaluate the presence of EPP

Limitations:

Also elevated in early and late iron deficiency, anemia of chronic disease and chronic lead poisoning

Another test for free protoporphyrin is Porphyrins, Serum Total

Follow-up:

To evaluate for lead poisoning, order whole blood lead testing

Test name: Cutaneous Direct Immunofluorescence, Biopsy

ARUP #: 0092572

Methodology: Direct Immunofluorescence

Use:

Biopsy of skin for unusual cutaneous presentations

Additional Tests Available

Test name: Porphyrins Profile, Plasma

ARUP #: 0092012

Methodology: High Performance Liquid Chromatography/Extraction and Scanning Spectrofluorometry

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