Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 40-15: Acute Intermittent Porphyria + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Unexplained abdominal crisis, generally in young women Acute central or peripheral nervous system dysfunction Recurrent psychiatric illnesses Hyponatremia Porphobilinogen in the urine during an attack +++ General Considerations ++ Acute intermittent porphyria is caused by partial deficiency of hydroxymethylbilane synthase activity, leading to increased excretion of aminolevulinic acid and porphobilinogen in the urine Genetics: mutation in the porphobilinogen deaminase gene Autosomal dominant inheritance It remains clinically silent in the majority of patients who carry a mutation in HMBS Characteristic abdominal pain may be due to abnormalities in autonomic innervation in the gut Cutaneous photosensitivity is absent Attacks precipitated by numerous factors, including drugs and intercurrent infections Hyponatremia resulting from inappropriate release of antidiuretic hormone and gastrointestinal loss of sodium +++ Demographics ++ Usually presents in adulthood and has serious consequences Clinical illness usually develops in women Symptoms beginning in the teens or 20s, but in rare cases after menopause + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Intermittent abdominal pain of varying severity, sometimes simulating an acute abdomen Absence of fever and leukocytosis Complete recovery between attacks Autonomic neuropathy Peripheral neuropathy, symmetric or asymmetric, mild or profound CNS manifestations include Seizures Altered consciousness Psychosis Abnormalities of the basal ganglia +++ Differential Diagnosis ++ Acute abdominal pain resulting from other cause, such as Appendicitis Peptic ulcer disease Cholecystitis Diverticulitis Ruptured ectopic pregnancy Familial Mediterranean fever Polyneuropathy resulting from other cause Guillain-Barré syndrome Lead or other heavy metal poisoning Psychosis resulting from other cause Syndrome of inappropriate antidiuretic hormone resulting from other cause Dark urine resulting from other cause (eg, alkaptonuria) + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Hyponatremia, often profound Freshly voided urine is of normal color but may turn dark upon standing in light and air Urine porphobilinogen increased during an acute attack Most families have different mutations in HMBS Mutation detection in the gene for porphobilinogen deaminase + Treatment Download Section PDF Listen +++ +++ Medications ++ Analgesics Intravenous glucose High-carbohydrate intake, a minimum of 300 g carbohydrate/day orally or intravenously Hematin up to 4 mg/kg intravenously once or twice daily Adverse consequences of hematin therapy include phlebitis and coagulopathy +++ Therapeutic Procedures ++ High-carbohydrate diet diminishes the number of attacks Withdrawal of the inciting agent Liver transplantation for extreme cases + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ ECG Electrolytes Glucose Mental status +++ Prevention ++ Avoidance of factors known to precipitate attacks, especially drugs (Table 40–1) Starvation diets must be avoided Hormonal changes during pregnancy can precipitate crisis ++Table Graphic Jump LocationTable 40–1.Some of the “unsafe” and “probably safe” drugs used in the treatment of acute porphyrias.View Table||Download (.pdf) Table 40–1. Some of the “unsafe” and “probably safe” drugs used in the treatment of acute porphyrias. Unsafe Probably Safe Alcohol Alkylating agents Barbiturates Carbamazepine Chloroquine Chlorpropamide Clonidine Dapsone Ergots Erythromycin Estrogens, synthetic Food additives Glutethimide Griseofulvin Hydralazine Ketamine Meprobamate Methyldopa Metoclopramide Nortriptyline Pentazocine Phenytoin Progestins Pyrazinamide Rifampin Spironolactone Succinimides Sulfonamides Theophylline Tolazamide Tolbutamide Valproic acid Acetaminophen Amitriptyline Aspirin Atropine Beta-adrenergic blockers Chloral hydrate Chlordiazepoxide Corticosteroids Diazepam Digoxin Diphenhydramine Guanethidine Hyoscine Ibuprofen Imipramine Insulin Lithium Naproxen Nitrofurantoin Opioid analgesics Penicillamine Penicillin and derivatives Phenothiazines Procaine Streptomycin Succinylcholine Tetracycline Thiouracil +++ Prognosis ++ Acute attacks may be life-threatening and require prompt diagnosis +++ When to Refer ++ For management of severe abdominal pain, seizures, or psychosis For preventive management when a patient with porphyria contemplates pregnancy For genetic counseling and molecular diagnosis +++ When to Admit ++ Patients should be hospitalized for an acute attack accompanied by mental status changes, seizure, or hyponatremia + References Download Section PDF Listen +++ + +Bissell DM et al. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862–72. [PubMed: 28854095] + +Fontanellas A et al. Emerging therapies for acute intermittent porphyria. Expert Rev Mol Med. 2016 Nov 2;18:e17. [PubMed: 27804912] + +O'Malley R et al. Porphyria: often discussed but too often missed. Pract Neurol. 2018 Oct;18(5):352–8. [PubMed: 29540448] + +Pinto RJ et al. Porphyrias: a clinically based approach. Eur J Intern Med. 2019 Sep;67:24–9. [PubMed: 31257150] + +Singal AK et al. Liver transplantation in the management of porphyria. Hepatology. 2014 Sep;60(3):1082–9. [PubMed: 24700519] + +Stölzel U et al. Clinical guide and update on porphyrias. Gastroenterology. 2019 Aug;157(2):365–81. [PubMed: 31085196]