An update of clinical management of acute intermittent porphyria

Abstract

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma.

Keywords: acute intermittent porphyria; heme; neuropathy; porphyria; treatment.

Figure 1

Precipitating factors and pathogenesis of an acute attack in AIP. Notes: Several exogenic and endogenic factors induce heme biosynthesis via direct or indirect activation of ALA synthase. In AIP patients with inherited deficiency of HMBS, this results in accumulation of neurotoxic porphyrin precursors (ALA and PBG) in tissues and circulation. Heme, the end product of heme biosynthetic pathway, regulates transcription of ALA synthase via negative feedback and can be used in the treatment of an acute attack. Abbreviation: AIP, acute intermittent porphyria.

Figure 2

Staging of an acute attack in connection with precipitating factors and recommendations of heme therapy. Note: Treatment with heme preparations: recommended (thin solid arrow), usually unnecessary (dotted arrow), influence of precipitating factors and connection with staging of acute attack (thick gray arrow). Abbreviations: CNS, central nervous system; d, days.