Complications Diagnosis Treatment Introduction Causes symptoms

Introduction Sickle-cell disease (SCD), or sickle-cell anaemia (or anemia) (SCA) or drepanocytosis, is an genetic disease characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various complications

The sickling occurs because of a mutation in the hemoglobin gene . The sickling occurs because of a mutation in the hemoglobin gene. Life expectancy is shortened. In 1994, in the US, the average life expectancy of persons with this condition was estimated to be 42 years in males and 48 years in females,[1] but today, thanks to better management of the disease, patients can live into their 50s or beyond.[2]

Sickle-cell disease occurs more commonly in people (or their descendants) from parts of tropical and sub-tropical regions where malaria was common. In areas where malaria is common, there is a fitness benefit in carrying only a single sickle-cell gene (sickle cell trait). Those with only one of the two alleles of the sickle-cell disease, while not totally resistant, are more tolerant to the infection and thus show less severe symptoms when infected.[

Sickle-cell anaemia is the name of a specific form of sickle-cell disease in which there is homozygosity for the mutation that causes HbS. Sickle-cell anaemia is also referred to as "HbSS", "SS disease", "haemoglobin S" from the two parents. In heterozygous people, who have only one sickle gene and one normal adult haemoglobin gene, it is referred to as "HbAS" or "sickle cell trait".

Rare forms of sickel cell disease Other, rarer forms of sickle-cell disease include sickle-haemoglobin C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia (HbS/β0). These other forms of sickle-cell disease are compound heterozygous states in which the person has only one copy of the mutation that causes HbS and one copy of another abnormal haemoglobin allele

What is anemia? Anemia is a disorder in which your blood has less than normal amounts of healthy red blood cells. In the most common kind, dietary anemia, this may be due to not enough iron and other nutrients that are needed to make red blood cells. Normal healthy red blood cells are made in the bone marrow and live for about 120 days, before being replaced. In sickle cell anemia, there are lower than normal amounts of red blood cells because sickle cells are more fragile and last only about 10 to 20 days. The bone marrow cannot make new red blood cells fast enough, leading to low levels of red blood cells and decreased oxygen delivered to the body.

Inheritance The types of haemoglobin a person makes in the red blood cells depend on what haemoglobin genes are inherited from his parents. If one parent has sickle-cell anaemia (SS) and the other has sickle-cell trait then there is a 50% chance of a child's having sickle-cell disease and a 50% chance of a child's having sickle-cell trait. When both parents have sickle-cell trait a child has a 25% chance of sickle-cell disease, as shown in the diagram.

Causes The gene defect is a known mutation of a single nucleotide (see single-nucleotide polymorphism - SNP) (A to T) of the β-globin gene, which results in glutamic acid being substituted by valine at position 6. Haemoglobin S with this mutation is referred to as HbS, as opposed to the normal adult HbA. The genetic disorder is due to the mutation of a single nucleotide, from a CTC to CAC codon on the template strand,

The sickle-cell disease occurs when the sixth amino acid (glutamic acid), is replaced by valine to change its structure and function. Valine is hydrophobic, causing the haemoglobin to collapse in on itself occasionally. The structure is not changed otherwise. When enough haemoglobin collapses in on itself the red blood cells become sickle-shaped.

. Sickle cells are stiffer and unable to squeeze through smaller blood vessels. They also stick together and form blood clots and clumps. Sickle cell anemia is an inherited, lifelong disease that does not have a cure

Signs& Symptoms 1-Vaso-occlusive crisis : The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis and often organ damage

2-Splenic sequestration crisis : are acute, painful enlargements of the spleen. The sinusoids and gates would open at the same time resulting in sudden pooling of the blood into the spleen and circulatory defect leading to sudden hypovolaemia. The abdomen becomes bloated and very hard. Splenic sequestration crises are considered an emergency. If not treated, patients may die within 1–2 hours due to circulatory failure.

3-Aplastic crisis: 4-Haemolytic crisis :

1-Overwhelming post-(auto)splenectomy infection (OPSI), 2-Stroke 3-Silent stroke

4-Decreased immune reactions due to hyposplenism . 5-Acute papillary necrosis in the kidneys. 6-During pregnancy, intrauterine growth retardation, spontaneous abortion, and pre-eclampsia.

7-Pulmonary hypertension (increased pressure on the pulmonary artery), leading to strain on the right ventricle and a risk of heart failure . 8-Chronic renal failure .