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.

Pathophysiology, Pharmacology and Treatment of Acute Intermittent Porphyria: A Patient Case Description and Recommendations from the Current Literature

“…Currently, in addition to glucose, the mainstay of therapy is intravenous hemin. 13 This therapy is the only available treatment that is specifically labeled for acute porphyria exacerbations and takes anywhere from 2 to 5 days to resolve symptoms. It is thought that hemin represses the synthesis of and directly inhibits ALAS.…”

Prospect and progress of gene therapy in acute intermittent porphyria

“…During acute attacks, patients typically complain of severe abdominal pain and have peripheral and autonomic neuropathy, neuropsychiatric manifestations, and in very severe cases paralysis and respiratory failure. If the disease is not promptly recognized, acute attacks can be life-threatening [12]. Current treatment options for AIP patients suffering from an acute attack aim to reduce ALAS1 activity, mainly by administrating hemin preparations or high concentrations of carbohydrates [12].…”

“…If the disease is not promptly recognized, acute attacks can be life-threatening [12]. Current treatment options for AIP patients suffering from an acute attack aim to reduce ALAS1 activity, mainly by administrating hemin preparations or high concentrations of carbohydrates [12]. In general treatment with hemin results in a gradual improvement of symptoms and repeat intravenous infusion over several days are commonly required to control an acute attack.…”

“…A reduction in the activity of this protein might represent an attractive strategy to control or to avoid the accumulation of the neurotoxic precursors. Currently, treatment for AIP attacks is based on the administration of hemin that reduces ALAS1 activity and heme precursor levels by negative feedback [12]. A potential strategy for the treatment of AIP could be based on the reduction of ALAS1 levels in hepatocytes.…”

Effects of hemin and hemodialysis in a patient with acute intermittent porphyria and renal failure

“…1 It is caused by the partial deficiency of porphobilinogen (PBG) deaminase, also known as hydroxymethylbilane synthase (HMBS), which is the third enzyme in the heme synthesis pathway, resulting in hepatic overproduction of the porphyrin precursors 5-aminolevulinic acid (ALA) and PBG as well as porphyrins. 2 The HMBS gene is a 10-kb gene located on11q23.3 and consists of 15 exons. To date, .400 HMBS gene mutations, predominantly point mutations, have been identified as responsible mutations for AIP.…”