Porphyrias

Clinical Background

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

Classification

Clinical features of the two most common porphyrias (acute intermittent porphyria, porphyria cutanea tarda)
- Acute intermittent porphyria (AIP)
  - Neurologic, abdominal signs and symptoms
  - Age – average onset is 20s
  - Sex – M<F
- Porphyria cutanea tarda (PCT)
  - Cutaneous signs and symptoms
  - Age – average onset in males is 40s
  - Sex – M>F
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 – predominantly transmitted as autosomal dominant disorders
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

Click here for 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 surgical 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
Pseudoporphyria
- Presents with cutaneous findings of porphyria cutanea tarda without biochemical markers
  - Nonsteroidal antiinflammatory drug ingestion
  - Tetracycline-class antibiotic ingestion
  - Monitor patient for underlying porphyria

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations	Follow Up
Porphobilinogen (PBG), Urine 0080260 Method: Ion Exchange Chromatography/Spectrophotometry	Rule out acute intermittent porphyria (AIP) or other acute attack types of porphyrias associated with neurologic and/or psychiatric symptoms	24-hour specimen is more sensitive	If test is negative, but high clinical suspicion still exists, repeat when symptoms are present
Aminolevulinic Acid (ALA), Urine 0080103 Method: Ion Exchange Chromatography/Spectrophotometry	Evaluate suspected presence of ALA dehydratase deficiency porphyria, other acute porphyrias, lead poisoning and hereditary tyrosinemia (PBG synthase testing)	24-hour specimen is more sensitive	If lead poisoning is a possibility, order whole blood lead testing
Porphobilinogen (PBG) Deaminase, Erythrocyte 0099550 Method: Enzymatic/Fluorometry	Useful in family studies to determine which members are at most risk for AIP More correctly termed Hydroxymethylbilane synthase	Best performed in association with a specimen from an unaffected family member Not recommended for diagnosis of an individual patient
Porphyrins, Fractionation & Quantitation, Urine 2002058 Method: High Performance Liquid Chromatography	Evaluate cutaneous photosensitivity to exclude or rule out porphyria cutanea tarda (PCT)	24-hour specimen is more sensitive	If test is negative, but high clinical suspicion still exists, repeat when symptoms are present
Porphyrins & Porphobilinogen (PBG), Urine 2002181 Method: High Performance Liquid Chromatography/Ion Exchange Chromatography/Spectrophotometry	Evaluate patients with suspected porphyria presenting with cutaneous and/or neurologic and psychiatric symptoms	24-hour specimen is more sensitive
Porphyrins, Fecal 0099824 Method: High Performance Liquid Chromatography	Distinguish among AIP, HCP, VP Monitor EPP, HCP, VP	Bacterial modification of fecal porphyrins is extensive Meat in diet may influence test results
Porphyrins, Serum Total 0080429 Method: Scanning Fluorometry	Monitor PCT Confirm VP	Does not differentiate specific porphyrin that is present
Zinc Protoporphyrin (ZPP), Whole Blood 0020605 Method: Hematofluorometry	Screening test for EPP	Also elevated in early and late iron deficiency, anemia of chronic disease and chronic lead poisoning Less specific than EP test	To evaluate for lead poisoning, order whole blood lead testing If ZPP is elevated order EP and/or serum porphyrins
Erythrocyte Porphyrin (EP), Whole Blood 0020610 Method: Extraction/Fluorometry	Evaluate the presence of EPP	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	To evaluate for lead poisoning, order whole blood lead testing
Cutaneous Direct Immunofluorescence, Biopsy 0092572 Method: Direct Immunofluorescence	Biopsy of skin for unusual cutaneous presentations	Characteristic pattern of staining but not specific