Canadian guidance for diagnosis and management of acute hepatic porphyrias

•AHP results from abnormal heme biosynthesis causing neurological symptoms during acute attacks.•Various triggers stimulate heme synthesis, elevate heme precursors and cause acute attacks.•Elevated ALA and PBG cause acute abdominal pain, seizures, hallucinations, and polyneuropathy.•A high index of suspicion is vital, and diagnosis requires a substantial increase in urine PBG.•Givosiran, an RNA silencer, suppresses production of ALAS and reduces ALA and PBG concentrations. Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy. Diagnosis is challenging due to a non-specific, variable presentation with symptoms mimicking other common conditions. Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, δ-aminolevulinic acid and porphyrins using a single random (spot) sample. However, many patients have complications due to delays in diagnosis and management. A novel small interfering RNA-based agent, givosiran, has demonstrated efficacy in reducing acute attacks in a recent Phase III trial, leading to its approval for the management of AHP. Early diagnosis is crucial for the timely introduction of disease-modifying treatments that reduce impairments, enhance quality of life, and extend survival. In this guidance, we aim to improve awareness and outcomes of AHP by making recommendations about diagnosis, monitoring, and treatment in Canada.