EPP Treatment Planning: Vitamin D, Glycine Transporter Inhibition, and Liver Monitoring

This episode, "EPP Treatment Planning: Vitamin D, Glycine Transporter Inhibition, and Liver Monitoring," follows the 15-year-old patient into treatment planning.

Dr. Bonkovsky says current guidelines call for strict sun avoidance and covering exposed skin. That means wide-brimmed hats, protection for the back of the neck, gloves, and opaque clothing, which tends to be hot and does not breathe well. Patients are usually low in 25-hydroxyvitamin D, and although there are no good controlled data supporting repletion, he recommends oral vitamin D until levels approach 30 nanograms per milliliter.

Turning to bitopertin, he describes a competitive inhibitor of the glycine-1 transporter that reduces glycine uptake into developing red cells, lowering production of ALA and, downstream, protoporphyrin. In the Phase 2 study in Australian adults, patients received 20 or 60 milligrams for 24 weeks. Whole blood protoporphyrin fell about 32% on the lower dose and about 58% on the higher dose, with good tolerance apart from dizziness after the first doses. In the placebo-controlled Phase 3 study, the higher dose lowered protoporphyrin by about 40% within one to two months. After the second month there was not a single phototoxic reaction. Time in sun rose even in the placebo group, so he prefers objective protoporphyrin measures over subjective endpoints. He considers this patient an appropriate candidate for expanded access.

On counseling, he stresses hepatitis A and B antibody testing, with booster vaccination if the hepatitis B surface antibody is below 10 milli-international units per milliliter. He also advises avoiding unnecessary drugs, especially those that cause cholestasis. Estrogens and oral contraceptives are a concern, and a copper IUD may be safer. She needs a baseline liver and gallbladder ultrasound and a FibroScan, and abnormal findings would justify closer follow-up and consideration of liver biopsy. He suspects bitopertin may forestall hepatopathy, though this is not yet demonstrated.

The next episode in this series, "EPP Case 2: Breakthrough Phototoxicity in a Young Construction Worker," introduces a 24-year-old outdoor worker whose job security now depends on controlling his symptoms.