Circadian rhythms in acute intermittent porphyria--a pilot study

Area of Science:

• Biochemistry
• Endocrinology
• Genetics

Background:

• Acute intermittent porphyria (AIP) is an inherited haem synthesis disorder.
• Active AIP involves hepatic haem deficiency and overproduction of ALA and PBG.
• Haem influences circadian rhythms, prompting investigation into AIP and circadian profiles.

Purpose of the Study:

• To evaluate circadian profiles in women with AIP.
• To determine if AIP affects circadian markers like cortisol, melatonin, and clock gene expression.

Main Methods:

• Measured serum cortisol, melatonin, ALA, and PBG over 21 hours in 10 women (6 with AIP, 4 controls).
• Assessed mRNA levels of clock-controlled genes and haem synthesis genes in peripheral blood mononuclear cells.
• Included postmenopausal women or those on hormone therapy.

Main Results:

• Active AIP subjects had higher PBG, lower/dampened cortisol oscillations, and trend for lower melatonin.
• Clock-controlled gene mRNAs increased at 5 a.m. and 11 p.m. in all subjects.
• ALAS1, ALAS2, and PBGD mRNA levels increased at 11 p.m. only in active AIP subjects.

Conclusions:

• Women with active AIP exhibit disturbed circadian markers.
• These circadian disturbances may contribute to AIP's clinical features.