Acute Hepatic Porphyrias: Review and Recent Progress

Area of Science:

• Biochemistry
• Genetics
• Internal Medicine

Background:

• Acute hepatic porphyrias (AHPs) encompass four inherited heme biosynthesis disorders characterized by acute neurovisceral symptoms.
• Delayed or missed diagnoses are common due to symptom overlap with other conditions.
• Acute intermittent porphyria, a severe AHP type, is more prevalent than previously believed, affecting approximately 1 in 1600 Caucasians, though with low clinical penetrance.

Purpose of the Study:

• To provide an updated review of the literature on AHPs.
• To discuss recent and emerging therapeutic advances for AHP management.

Main Methods:

• Literature review focusing on AHP diagnosis, triggers, and treatments.
• Discussion of novel therapeutic strategies, including RNA interference targeting ALA synthase-1.

Main Results:

• AHPs present with episodic neurovisceral symptoms, primarily in females aged 14-45.
• Diagnosis relies on elevated urinary porphyrin precursors (ALA and porphobilinogen).
• Intravenous heme therapy is crucial for acute attacks; genetic counseling and monitoring are recommended for patients and relatives.

Conclusions:

• Current management involves prompt heme therapy, trigger avoidance, and regular monitoring.
• Newer treatments, such as small interfering RNA (siRNA) targeting hepatocytes, are under development.
• These novel therapies may significantly reduce or eliminate the need for liver transplantation for AHPs.