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acute intermittent porphyria (AIP); Swedish porphyria

Also see porphyria. Etiology: -> numerous drugs can precipitate attacks including: a) barbiturates b) diazepam c) chlordiazepoxide d) methyldopa e) oral contraceptives f) sulfonamides [5,6] g) phenytoin [5,6] Epidemiology: -> almost never before puberty Pathology: 1) pathophysiologically, the disease poses a riddle a) derangement of porphyrin metabolism is confined to the liver which anatomically appears normal b) the pathologic findings are restricted to the nervous system 2) circulating neurotoxic metabolite is suspected but has not been identified 3) Enzyme deficits include decreases in: a) uroporphyrinogen I synthase (porphobiliogen deaminase) b) aminolevulinic acid dehydratase Genetics: - autosomal dominant - associated with defects in uroporphyrinogen I synthase (porphobiliogen deaminase) Clinical manifestations: 1) colicky abdominal pain often associated with a) vomiting b) constipation c) fever d) leukocytosis 2) hypertension 3) tachycardia 4) peripheral neuritis 5) behavioral changes 6) psychosis Laboratory: 1) elevated urinary aminolevulinic acid (ALA) 2) elevated urinary porphobilinogen - red-tinged urine due to porphyrins [5,6] 3) hyponatremia (SIADH) 4) liver function abnormalities 5) transient elevation of bilirubin 6) transient elevation of alkaline phosphatase Complications: -> clinical presentation frequently leads to laparotomy Management: 1) prognosis - lifelong disease - good prognosis if precipitating factors are avoided - recovery from an acute attack depends upon neuronal injury - may be rapid 1-2 days if therapy is prompt - severe motor neuropathy may require months to years for recovery 2) pharmaceutical agents - narcotic analgesics for abdominal pain - phenothiazines (Compazine) for nausea - chloral hydrate for insomnia - low doses of benzodiazepines for anxiety are probably safe - parenteral nutrition if oral feeding is not possible - intravenous glucose (300 g/day) had been recommended in the past - intravenous heme: - 3-4 mg IV QD for 4 days - begin as soon as possible after attack - preparations: - hematin (Abbott) - heme albumin - heme arginate (Leiras Oy, Turka Finland) - heme albumin & arginate chemically stable & less likely than hematin to produce phlebitis or anticoagulant effect - luteinizing hormone-releasing hormone (LHRH) analog for women with attacks linked to menstrual cycle (not FDA approved) - goserelin

Related

delta-aminolevulinate; 5-aminolevulinic acid; aminolevulinic acid (ALA) delta-aminolevulinic acid dehydratase; ALADH; porphobilinogen synthase (ALAD) porphobilinogen porphobilinogen deaminase; PBG-D; hydroxymethylbilane synthase; HMBS; pre-uroporphyrinogen synthase (HMBS, PBGD, UPS) safe & unsafe drugs in acute intermittent porphyria (AIP), variegate porphyria (VP) & hereditary coproporphyria

General

porphyria

Properties

ACCUMULATION: aminolevulinate porphobilinogen DEFICIENCY: porphobilinogen deaminase delta-aminolevulinic acid dehydratase

Database Correlations

OMIM 176000

References

  1. Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 1012
  2. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 172
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2154-56
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 179
  5. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862-872. PMID: 28854095 Review. https://www.nejm.org/doi/pdf/10.1056/NEJMra1608634
  6. NEJM Knowledge+ Hematology