Intractable Rare Dis Res. 2020;9(4):205-216. (DOI: 10.5582/irdr.2020.03089)

Therapeutic strategies for acute intermittent porphyria

Zhao LL, Wang XY, Zhang XN, Liu XT, Ma NZ, Zhang YR, Zhang SY


Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by mutations in porphobilinogen deaminase (PBGD), the third enzyme of the heme synthesis pathway. Symptoms of AIP usually manifest as intermittent acute attacks with occasional neuropsychiatric crises. The management of AIP includes treatment of acute attacks, prevention of attacks, long-term monitoring and treatment of chronic complications. Intravenous injection of heme is the most effective method of treating acute attacks. Carbohydrate loading is used when heme is unavailable or in the event of mild attacks. Symptomatic treatment is also needed during attacks. Prevention of attacks includes eliminating precipitating factors, heme prophylaxis and liver transplantation. New treatment options include givosiran (siRNA) to down-regulate ALA synthase-1 (ALAS1) and the messenger RNA of PBGD (PBGD mRNA) delivered to the liver cells of patients with AIP. Long-term monitoring of chronic complications includes regular liver-kidney function and hepatocellular carcinoma (HCC) screening.

KEYWORDS: acute intermittent porphyria, heme, carbohydrate loading, givosiran (siRNA), mRNA therapy

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