Abstract
Background
Acute intermittent porphyria (AIP), is one of the acute porphyrias resulting from deficient activity of a distinct enzyme in the heme biosynthetic pathway. Porphobilinogen deaminase, is the enzyme in AIP with approximately 50% activity1. This predisposes individuals to factors exacerbating the disease, including drugs inducing heme synthesis and cytochrome P450 enzymes, steroids, dieting, smoking, stress, and infection. Clinically, AIP is characterized by visceral, autonomic, peripheral, and CNS involvement, leading to varying degrees of intermittent and life-threatening symptoms. Despite avoidance of these factors, frequent attacks may persist due to unidentified modifier genes or environmental/endogenous factors1. Recurrent noncyclic attacks may be prevented by weekly or biweekly infusions of hemin2.
Objective
To report the results of the prevention of acute life-threatening attacks of AIP by a multidisciplinary team leading to a 50–100% decrease in patient hospitalizations.
Methods
Three patients were diagnosed with AIP on the biochemical basis of increased urinary porphobilinogen and aminolevulinic acid levels. All patients required hospitalization over 3–5 years due to severe abdominal pain and inability to maintain caloric intake and hydration. Due to recurrent attacks, hemin 313 mg was initiated on a prophylactic basis and frequency of administration was dependent on activity of their disease. All 3 patients served as their own control and the outcome of hemin prophylaxis was measured by patient symptoms, narcotic requirements, physical examination, and hospitalizations.
Results
Three patients (1 female, 2 male) with a mean age of 58 years had recurrent attacks of AIP. Patient #1 was hospitalized monthly over 5 years and received hemin for 10 days during acute attacks. Hemin infusions 1/month was initiated, and hospitalizations decreased by 50% until discontinued due to severe cardiomyopathy (unknown if related to porphyria). She expired in hospice care. Patient #2 was classified as a drug seeker for 3 years. After diagnosis, he was hospitalized almost monthly for 3–5 days during acute attacks over 2–3 years. Hemin was infused 1/month and symptoms persisted. Infusions were increased to 2/month. Symptoms and narcotic requirements have decreased and he has not been hospitalized. Patient #3 experienced acute attacks during stress, increasing due to business travel abroad. He was hospitalized 4 times in 3 years. As a nurse, he self-administers 1/month and in the office approximately every 2–3/months. 2 of 3 patients experienced phlebitis during infusions and receive via a portacath with no further adverse events. 2 of 3 patients have not required hospitalizations for acute attacks, symptoms have decreased and/or resolved, as well as narcotic requirements.
Conclusions
The experience in management of these three patients demonstrates the safety and effectiveness of hemin as a prophylactic agent in AIP. Most patients will require treatment 1–2 times/month and can avoid painful crisis and hospitalizations.
PATIENT DATA, TREATMENT, AND RESULTS Patient Age Sex Yr Diagnosis Presenting Sxs Txment Frequency Hospitalizations 1 66 F 1990 Abdominal Pain, Difficulty Urinating 1 month/5yrs 50% ↓ 2 52 M 1996 Abdominal Pain, Neuropathic Sxs 2 month/2 yrs 100%↓ 3 56 M 2002 Abdominal Pain, Paresthesias 1 month/8 mos 100%↓
Galactosemia: Towards Pharmacological Chaperones
