Porphyria, Acute Intermittent

Key Features

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

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

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

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

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 ...