Congenital Erythropoietic Porphyria - Research Paper Example

CEP, or congenital erythropoietic porphyria is an autosomal recessive trait, which causes the patient to have an enlarged spleen and liver, reddish urine, bones and teeth as well as lesions on the skin that react to UV light due to the excess porphyrin deposits (Bishop et al., 2010, p. 1062). However, another disease, AIP or acute intermittent porphyria could pose as CEP due to some similarities in patient symptoms. Initially, patients that were affected were suspected to have CEP since there were the usual symptoms such as the reddish discoloration of teeth as well as the urine, and pink fluorescence of bones under UV light due to deposition of porphyrin and other precursors (Clavero et al., 2009, p. 585).

However, if molecular and tissue analyses would be employed, CEP and AIP can be differentiated from each other, with CEP being an autosomal recessive disease and AIP a dominant one. This paper would be about some studies on congenital erythropoietic porphyria (CEP), as well as some descriptions of the disease at the genetic level. The first main topic is about the molecular aspect of CEP as a disease. The most common form of mutation of the UROS gene located at locus 10q25.3-26.3 is the C37R mutation, which is fairly common.

Other mutations such as non-sense mutations, splicing in certain cites, deletions and insertions as well as other complex rearrangement of sequences at chromosomal locus 10q25.3-26.3 occur and create the CEP phenotype (Bishop et al., 2010, p.1068). In a study on the expression of CEP model expressions in mice, Bishop et al. (2011, p. 751) were able to quantify the approximated enzymatic activities of the UROS enzyme in livers of normal mice and CEP-affected mice. It is hypothesized that since mice are animals with shorter lifespan and thus have several generations in a short period of time, the causative mechanisms of the defective UROS gene would be easier to identify.

Also, since the disease would be following the Mendelian Pattern, bearers of the homozygous recessive genotype would show disease symptoms while heterozygous and homozygous dominant would be fairly normal. Meanwhile, in a study about CEP in cats, a publication regarding the discovery of a feline model for CEP was released (Clavero et al., 2010, p. 382). Compared to a previous study, which had cats with AIP instead of CEP, the new proband for this study had PBG and ALA levels which are in normal detectable amounts, with elevated URO I and COPRO levels as well as abnormal UROS activity, much like in human and mice CEP counterparts.

Via amplification of the suspected mutated sequences, aside from a shorter polypeptide (one cystein shorter), feline UROS sequence was fairly similar to the previously reported human and mouse. The double-mutant had reduced enzymatic activity, caused by two amino acid substitutions, making the protein product unable to fold in a stable manner, thereby causing reduced activity of the mutated enzyme, as compared to either single mutant or normal enzymes (Clavero et al., 2010, p. 387). Three genotypes were produced after mating several strains and generations of mice: homozygous recessive mice having the CEP gene had a genotype of C37R/C37R, a heterozygote C37R/V99L expresses a milder form of the disease, and a homozygous dominant genotype V99L/V99L exhibits the normal phenotype.

Blood sampling for analyses of presence of porphyrin and other precursors were done, as well as histology of the liver and the spleen