Congenital Erythropoeitic Porphyria ( Cep )

The working diagnosis is that this patient is suffering from Angioedema as a result of Anaphylaxis and developing Urticaria. Angioedema is the swelling of deep layers of the skin due the accumulation of fluid, symptoms of Angioedema include swelling of the eyes, lips, hands and feet.

All diseases grouped under porphyria are disorders of heme biosynthesis, the deficiency of one of the enzymes which are necessary for the production of heme. Heme includes hemoglobin, myoglobin, cytochromes, and other heme-containing proteins. These are found in all organs within the body, and they are most active in the liver and bone marrow. Due to this enzyme deficiency, the result is the accumulation of certain pathway intermediaries. Porphyria diseases can be categorized based on where the primary site of overproduction occurs. If the accumulation of porphyrins occurs in the liver then this is considered to be hepatic, and if the accumulation occurs in bone marrow then it is categorized as erythropoietic.

(TCO 6) Which of the following is a genetic disorder resulting in debilitating protein abnormalities?

I was diagnosed with Henoch-Schonlein purpura (HSP) when I was five years old. This is a rare disease that occurs mostly in children around the ages of two to six years old. The disease causes bleeding in your joints, the small vessels under your skin, your intestines, and your kidneys, leading to bruising and other issues. When this disease makes it to your kidneys, the results can be disastrous and require medical treatment, but if caught in time, the disease will rarely leave the patient with any serious kidney damage. Its progression is rapid. Overnight, my body began to bruise as if someone had beaten me. Every joint in my wrists, ankles, hips, shoulders, even my toes and fingers, began to bruise and became swollen. I had bruises all over

AS is caused by a deletion or mutation on the maternal chromosome 15, alteration in UBE3A gene, paternal uniparental disomy, translocation, or mutation in the gene that activates UBE3A gene. PWS is a deletion or mutation on the paternal chromosome 15, uniparental disomy, or translocation. The loss of the SNORD116 gene on chromosome

Hennekam syndrome, a rare autosomal recessive disorder, is characterized by lymphangiectasia along with mental retardation.27 Limb and facial edema may be apparent at

Starting the experiment, researchers began to gene code the human CELSR1 region. Figure 1 represents the 46 TGTG sequences and the three TGTGTG dinucleotide repeats. In reference to spina bifida cases, researchers were able to identify two repeated dinucleotides: TG-insertion (c.5050-5051insTG) which created a stop codon on the 1706th amino acid and TG-deletion (c.5719-5720delTG) which created a stop codon on the 1944th amino acid (Figure 1). Figure 1 and Table 1 also represent the data that was collected for the identified 11 missense Single Nucleotide Variants (SNVs)

They have shown that there is complete cosegregation between the 605(C→A) nucleotide substitution and people affected by this syndrome. Located in the homeobox coding region in exon 2, the aftermath of this mutation was a stop codon at amino acid position 37 of the homeodomain. The conjectural lost part of the protein was known to be significant for protein stability (helix II) (Hu et al. 1998) and DNA binding (helix III) (Isaac et al. 1995). The abbreviated protein thus formed lacked in part of the homeodomain and the entire C-terminal region was unable to bind to DNA causing the dominant phenotype of Witkop syndrome through haploinsufficiency, instead of a dominant-negative mechanism. This was also substantiated by a study where a missense mutation (R196P) in the homeodomain of MSX1 causes familial tooth agenesis

Polycythemia Vera is the most common form and the frequency of the condition is 1-2 individuals affected per over 100,000. The problem is often linked to a gene defect called JAK2V617F and the cause/mechanism of the defect is unknown. Another form of polycythemia, Chuvash, causes abnormalities in the VHL protein and prevents HIF-1α from binding and degrading under normal oxygen conditions. Thus, even under normoxic conditions, an individual would have elevated HIF, EPO, and red blood cell levels (i.e. erythrocytosis). Early stages of polycythemia do not show any signs, but as the disease progresses symptoms start to appear. Individuals may get frequent headaches, weakness, dizziness, and/or tinnitus. Other symptoms include excessive itching, enlarged spleen and/or liver, hypertension, thrombosis, hemorrhaging, and sometimes obstruction of hepatic

Patients also start to develop small red spots, or telangiectasia’s on the face, mouth, fingers, and in the gastrointestinal tract. A high number of HHT patients will also have or develop artery malformations (AVM’s) in one or ore body organs, where capillaries between arteries and veins are missing. Other common symptoms of HHT include: shortness of breath, exercise tolerance, fatigue, migraine headaches, seizures, abdominal pain, leg swelling, intestinal bleeding, anemia. Also very small proportion of patients have multiple benign polyps in the large intestine, which may bleed or transform into colorectal cancer. A similarly small proportion experiences pulmonary

Proteins play a critical role in normal human function and are made up of a sequence of amino acids that have to be precise, to allow for proper folding to a functional three dimensional structure (confirmation). This sequence is coded in the DNA in genes and hence any changes through mutation or allele combinations can cause a change in the protein(s) coded, resulting in a diseased state. Such a case is a disease called Cerebroarterial Amyloidosis, Icelandic type (CAI) that arises from a mutation on chromosome 20 in the CST3 gene located in the short arm of the chromosome (20p11.21).1 It is an autosomal dominant hereditary disease and the mutated gene leads to the protein translated (cystatin C) having a leucine being substituted with a Glutamine

Erdheim-Chester Disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by foamy infiltrates of the soft tissue and bone, with a histopathology that reveals CD68+, CD1a-, and S100- histiocytes densely infiltrating bone, lymph nodes, retroperitoneum, and systemic vasculature. Although no therapy has been designated as standard, a variety of chemotherapeutic options exist for management in adults. Cladribine (2-chlorodeoxyadenosine) is a metabolite that predominantly affects blood cells by mimicking adenosine nucleosides, inhibiting adenosine deaminase and thus disrupts the ability of the cell to repair DNA. In this paper we report three patients with varying sites of disease who achieved remission following treatment with Cladribine. Although the efficacy of Cladribine has been demonstrated in patients with ECD who primarily exhibited neurological symptoms, we present three patients in whom significant responses were achieved in disease distributed in long bones, pericardium, and retroperitoneum.

The topic of my research paper is porphyria. Porphyria is a genetic disorder which is also known as “the vampire disease.” The word “Porphyria” came from the Greek word πορφύρα, meaning “purple color.” In 1841, scientists discovered the purplish red substance which is called porphyrin in human blood. This substance is important because it produces heme which carries the oxygen in the blood. Then in 1874, Dr. J. H. Schultz found a 33-year-old man who had extreme sensitivity on skin, large area of spleen and purplish urine. This man is believed to be the first victim of porphyria. The name of this disease was given by Dr. J. H. Schultz. 14 years later scientist called Joseph Stokvis found hematoporphyrins in the urine of his patient who suffered

Figure 3. Roles of eNOS in atherosclerosis. The structure of NOS is a homodimer with each monomer including an oxygenase dominion and a reductase dominion. The oxygenase dominion comprises the binding locates for heme, L-arginine (the substrate) and the cofactor tetrahydrobiopterin (BH4), an important determining factor of eNOS activity. In vascular disease states such as diabetes, hypertension, or hypercholesterolemia, superoxide generation by oxidases is significantly increased. Peroxynitrite and other reactive oxygen species oxidize BH4, through the BH3 radical to BH2 and biopterin, which decreases the bioavailability of BH4 and stimulates eNOS uncoupling. This form of eNOS no longer produces NO, but instead produces superoxide.

More recently, loss of CEP55 function due to presence of truncated mutation in the C-terminal region of CEP55 (p.S425X) has been shown to cause a novel autosomal recessive syndrome affecting neuronal mitosis called MARCH (Multinucleated neurons, Anhydramnios, Renal dysplasia, Cerebellar hypoplasia and Hydranencephaly) [274]. Hydranencephaly is a congenital anomaly wherein the cerebral hemisphere of the brain is replaced by fluid-filled cyst. Frosk et al. reported presence of homozygous nonsense mutation in CEP55 which resulted in truncation of CEP55 mRNA in patient sample. They also expressed the truncated form of CEP55 in COS-7 cells and observed that the truncated protein (~40 amino acid short), fails to localize to the midbody that