89: The Porphyrias

Acute Porphyrias

Key Points

• Disease summary:

  • All porphyrias are diseases resulting from abnormalities of heme biosynthesis.

  • The four acute porphyrias, in descending order of prevalence, and their inborn enzymatic errors are intermittent acute porphyria (IAP; ∼50% reduction in porphobilinogen deaminase), variegate porphyria (VP; ∼50% reduction in protoporphyrinogen oxidase), hereditary coproporphyria (HCP; ∼50% reduction in coproporphyrinogen oxidase), and delta-aminolevulinic acid (ALA) dehydratase deficiency porphyria (ADP; >95% reduction in ALA dehydratase).

  • IAP, VP, and HCP are inherited as autosomal dominant syndromes; ADP is an autosomal recessive syndrome.

  • Carriers of the gene for IAP, VP, and HCP may have no manifestations or chronic but low-level manifestations (the majority), or acute attacks that may be life threatening.

  • Homozygotes for the gene causing ADP may be symptomatic frequently, commencing often in childhood. Heterozygotes may be liable for developing lead toxicity.

  • Precipitants of the acute attack are intercurrent illness, certain medications, environmental agents (eg, impurities in drinking water, organic solvents), dietary restriction, or hormonal fluctuations in the menstrual cycle. Often the cause is unknown.

• Hereditary basis

  • IAP, HCP, and VP—autosomal dominant, with low penetrance resulting from variable environmental stimuli. ADP—autosomal recessive; apparently exceedingly rare. Penetrance may approach 100%.

• Differential diagnosis (Table 89-1)

  • Manifestations are often nonspecific, and misdiagnosis is common.

  • Abdominal pain consistent with the pain of an acute porphyria is common in constipation, acute gastroenteritis, functional bowel disease, celiac disease, inflammatory bowel disease, pseudomembranous colitis (Clostridium difficile toxin), gall bladder disease, pancreatitis, etc.

  • The sympathomimetic manifestations resemble those in pheochromocytoma, thyrotoxicosis, delirium tremens, and neuroleptic malignant syndrome.

  • Ascending polyneuropathy is seen in Guillain-Barré syndrome.

  • The cutaneous manifestations of HCP and VP resemble those of porphyria cutanea tarda (PCT).

  • The possibility that an acute porphyria is responsible for the manifestations of an acute event can be resolved definitively by finding highly abnormal quantities of porphyrin precursors porphobilinogen (PBG) and/or ALA in a spot urine obtained during this attack. Marked elevations of PBG and/or ALA are the rule during an acute attack. Normal urinary PBG and/or ALA excretion rules out an acute porphyric attack.