Porphyrias

Porphyrias

 

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

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 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

Diagnosis

  • Laboratory testing
    • Serum, urine, fecal and bile testing for porphyrias based on clinical manifestations (see Porphyria Testing algorithm)
    • Testing most accurate when symptoms are present 
    • Skin biopsy for unusual cutaneous presentations

Differential Diagnosis

  • Neurological
    • Depression
    • Seizure disorder
  • Abdominal
    • Acute surgical abdomen
  • Cutaneous symptoms
    • Pemphigoid
    • Pemphigus
    • Steven's Johnson/Toxic Epidermal Necrolysis (TEN)
    • Polymorphous light eruption

See Also