Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the bodys organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood. Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda, although it can also be caused if two different mutations occur at the same locus. Symptoms and signs
Porphyria cutanea tarda (PCT) is recognized as the most prevalent subtype of porphyritic diseases.PCT is characterized by onycholysis and blistering of the skin in areas that receive higher levels of exposure to sunlight. The primary cause is a deficiency of uroporphyrinogen decarboxylase (UROD), a cytosolic enzyme that is a step in the enzymatic pathway that leads to the synthesis of heme. Behind the direct cause there are a number of genetic and environmental risk factors.Patients who are diagnosed with PCT typically seek treatment following the development of photosensitivities causing blisters and erosions on exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. Healing is slow and leaves scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations include hyperpigmentation (similar to a tan) and hypertrichosis (mainly on the cheeks) also occur.
Mannosidase I creates a Man5GlcNAc2-structure on the protein, but note that this has a different structure than the one made on LLO. Next, a GlcNAc residue forms GlcNAc1Man5GlcNAc2, the substrate for a-mannosidase II (aManII). aManII then removes two Man residues, creating the substrate for GlcNAc transferase II, which adds a GlcNAc to the second Man branch. This structure serves as substrate for additional galactosylation, fucosylation and sialylation reactions. Additionally, substitution with more GlcNAc residues can yield tri- and tetra-antennary molecules.Not all structures are fully modified, some remain as high-mannose structures, others as hybrids (one unmodified Man branch and one modified), but the majority become fully modified complex type oligosaccharides.In addition to glycosidase I, mutations have been found:
in MGAT2, in GlcNAc transferase II (CDG-IIa)
in SLC35C1, the GDP-Fuc transporter (CDG-IIc)
in B4GALT1, a galactosyltransferase (CDG-IId)
in COG7, the conserved oligomeric Golgi complex-7 (CDG-IIe)
in SLC35A1, the CMP-sialic acid (NeuAc) transporter (CDG-IIf)However, the use of >100 genes in this process, presumably means that many more defects are to be found. Diagnosis
Classification
Historically, CDGs are classified as Types I and II (CDG-I and CDG-II), depending on the nature and location of the biochemical defect in the metabolic pathway relative to the action of oligosaccharyltransferase. The most commonly used screening method for CDG, analysis of transferrin glycosylation status by isoelectric focusing, ESI-MS, or other techniques, distinguish between these subtypes in so called Type I and Type II patterns.Currently, twenty-two CDG Type-I and fourteen Type-II subtypes of CDG have been described.Since 2009, most researchers use a different nomenclature based on the gene defect (e.g.