Elliptocytosis, Spherocytosis, HNPCC, Diabetes Insipidus

Hereditary and inherited diseases occur due to chromosomal aberration or change. These rare conditions are primarily caused by genetic mutation and a change in the chromosome. Hereditary spherocytosis, a type of congenital hemolytic anaemia, is one such example. A genetic mutation coding for a structural membrane protein leads to the formation of the spherical shape of the erythrocyte, impacting the entire blood circulation. Other examples of diseases caused by genetic mutation include elliptocytosis, diabetes insipidus, and HNPCC. The topic gives details of the occurrence of the conditions and how it impacts a person’s health.

Hereditary Spherocytosis

• It is a congenital hemolytic disorder where genetic mutation leads to a phenotypic change in the erythrocytes. It changes the shape of the erythrocytes into a spherical shape

• Hereditary spherocytosis leads to a change in the morphology of the erythrocytes. Hence it interferes with the cell’s ability to be flexible during the circulation. The cell’s shape makes it more prone to rupture under mechanical or osmotic stress

• Mutations in nearly five genes cause hereditary spherocytosis. The genes have instructions for producing proteins found on the RBC membrane. The proteins help maintain the structure, allow flexibility, and allow travel of the RBC from large blood vessels to smaller blood vessels

• The mutations in the proteins of the RBC lead to hereditary spherocytosis Gallagher. The mutation leads to the production of misshapen red blood cells, which are spherical instead of biconcave disc-shaped

• The majority of hereditary spherocytosis occurs due to mutations in the ANK1 gene. However, there are other genes too, which contribute to the condition

• The hereditary spherocytosis Gallagher report states that five genes cause the genetic mutations. It is caused due to defects in the genes that code for red blood cell proteins spectrin (alpha and beta), ankyrin, band three protein, protein 4.2, and a few other RBC membrane proteins

Hereditary Elliptocytosis 

• It is also known as ovalocytosis and is an inherited blood disorder that leads to the formation of RBC (red blood cells) elliptical

• The elliptocytosis causes are due to genetic mutation, which causes red-cell membrane defect. In many cases, it leads to the occurrence of hemolytic anaemia. 

• The hereditary elliptocytosis is caused due to a defect in either the structure or quantity of the cytoskeletal proteins responsible for maintaining the biconcave shape of RBC. The most common elliptocytosis causes are mutations in either the alpha or beta-spectrin proteins. It even occurs due to mutations in cytoskeletal proteins like glycophorin and band 4.1

• Some of the symptoms are mild anaemia, leg ulcers, jaundice, splenomegaly, etc. Almost 90% of the disorder falls under the asymptomatic category

HNPCC

• It stands for hereditary nonpolyposis, colorectal cancer, or Lynch syndrome. It is an autosomal dominant genetic condition that puts the affected individual at high risk of colon cancer. It also increases the risk of other forms of cancer like endometrial cancer, small intestinal cancer, and cancer of the ovary, stomach, urinary tract, brain, skin, etc

• The inherited mutations impair the DNA mismatch repair and increase the risk for various forms of cancer

• It is caused by an abnormality in a gene that is typically involved in the repair of the body’s DNA. There are almost five mismatch repair genes that are associated with HNPCC. If the genetic damage is not repaired, it can lead to colon cancer

• The HNPCC is caused due to defective DNA mismatch repair gene causing an elevated rate of single nucleotide change and microsatellite instability

Diabetes Insipidus 

• It is a condition that causes an imbalance of fluids in the body leading to a large urine volume. The rare disorder causes the body to make too much urine, and hence people need to urinate frequently, a condition called polyuria

• Diabetes insipidus is of different types, and each occurs due to a different cause. Central diabetes insipidus is caused due to vasopressin hormone, while nephrogenic DI is caused due to inability of the kidney to respond properly to vasopressin. This occurs due to a defect in the kidneys’ structure, which can either be an inherited disorder or a chronic kidney disorder

• Dipsogenic diabetes insipidus is caused due to excessive fluid intake caused due to damage to the hypothalamic thirst mechanism. This is caused due to damage to the thirst-regulating mechanism in the hypothalamus. Gestation DI occurs during pregnancy. It occurs due to excessive production or impaired clearance of the enzyme vasopressin

Conclusion 

There are certain conditions caused by genetically inherited disorders or gene mutations. Hereditary spherocytosis is an inherited genetic disorder which causes a phenotypic change in the RBC due to gene mutation. It changes the shape of the RBC from biconcave to spherical shape. The elliptocytosis causes a change in the shape of RBC forming an elliptical shape, and hence is due to genetic mutation. Conditions like HNPCC and diabetes insipidus are due to genetic mutation causing the conditions. HNPCC is an autosomal genetic condition that puts one at high risk of colon cancer. Diabetes insipidus is a rare disorder that causes the production of a large volume of urine. These are some of the conditions that occur due to genetic mutation.