PCT, the most common type of porphyria worldwide, is caused by the deficiency of the enzyme UROD
, a crucial enzyme in heme biosynthesis, which results in an accumulation of photosensitive byproducts such as uroporphyrinogen which leads to the fragility and blistering of sun-exposed skin.
Especially significant, Schuetz said, was the finding that MYCN-driven leukemias with the most over-activated UROD were far more lethal.
One would be to target UROD, which would reduce heme biosynthesis.
4] Human genes: ACTB, actin, beta; B2M, beta-2-microglubulin; DEFA3, defensin, alpha 3, neutrophil-specific; SRGN, serglycin; HBB, hemoglobin, beta; UROD
, uroporphyrinogen decarboxylase; ITGA2B, integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41); ITGB3, integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61); CD34, CD34 molecule; CD3E, CD3e molecule, epsilon (CD3-TCR complex); CD4, CD4 molecule; CD8A, CD8a molecule; CD19, CD19 molecule.
Gevirtz to the American Society of Anesthesiologists, however, UROD can cause drastic physical changes in the patient and should only be done with an anesthesiologist present.
Underscoring the need for an anesthesiologist to direct the procedure, Gevirtz cites analysis of the deaths of seven patients who underwent UROD.
Working with the most toxic dioxin,TCDD--now generally considered the most porphyrin-disrupting compound as well--Lavinia Cantoni and her colleagues at the Institute of Pharmacological Research Mario Negri in Milan, Italy, have found that the liver, and secondarily the kidney, appear to be the main sites of UROD
impairment by liver-damaging PAHs.
fPCT and sPCT cases were discriminated by mutation analysis of the UROD gene (Christianson et al.
The reported findings thus imply that mutations in the HFE gene could constitute, at least in part, a genetic basis of PCT in patients lacking mutations in the UROD gene.