Genetic Syndromes: Sickle Cell Disease, and Severe Combined immunodeficiency (SCID) For Class 11th and 12th

Genetic Syndromes: Sickle Cell Disease, and Severe Combined immunodeficiency (SCID) For Class 10th,11th and 12th

Sickle cell disease

Sickle cell disease (SCD), which is the result of homozygous and compound heterozygote inheritance of a mutation in the -globin gene, was originally described by Herrick in 1910, although reports suggested that the ailment had been described earlier. A single base-pair point mutation (GAG to GTG) causes the hydrophobic amino acid valine to replace the hydrophilic amino acid glutamic acid in the sixth position of the -chain of haemoglobin, resulting in haemoglobin S. (HbS). SCD is the first disease to be molecularly characterised, as described by Pauling, and was confirmed to be caused by a single amino acid substitution by Ingram almost 70 years ago. Despite a well-defined Mendelian inheritance, phenotypic variation in clinical presentation is a distinctive feature of SCD. When foetal haemoglobin (HbF) lowers toward the adult level by five to six months of age, SCD is a multi-organ, multi-system condition with both acute and chronic consequences.


The most common form of SCD is homozygous HbS inheritance, often known as sickle cell anaemia (SCA). The proportion varies depending on the country of origin. The co-inheritance of HbS and HbC, also known as HbSC, is the second most frequent kind of SCD and is most widespread in Western Africa, particularly in Burkina Faso and Mali as well as the coastal nations like Ghana, Benin, and Western Nigeria. Depending on the genetic lesion on the thalassaemia component, co-inheritance with thalassaemia results in a sickle thalassaemia genotype (HbS/o or HbS/+). Both mild and severe clinical manifestations of homozygous SCD (HbS/HbS) are possible. While individuals with HbS/+-thalassaemia depending on the -globin mutation are associated with different phenotypes from mild to severe phenotypic SCD, those with HbS/o-thalassaemia have a more severe course of disease similar to homozygous SS patients.


One of the most prevalent hereditary, fatal diseases affecting people is SCD, which primarily affects those with African, Indian, and Arab ancestry. Over 300,000 births per year are thought to occur in sub-Saharan Africa (SSA), with Nigeria and the Democratic Republic of the Congo bearing the most load. Compared to 1/400 African Americans, the gene frequency is highest in West African countries, where 1 in 4 to 3 (25–30%) people carry the HbS gene. It varies in European groups. Migration from nations with high SCD incidence is contributing to an increase in SCD prevalence in industrialised countries. Similar to France, the UK is projected to have around 14,000 people living with SCD, whereas populations from Africa are growing in Italy and Germany. The age distribution of SCD is evolving from a childhood disorder pattern where patients now live into maturity and old life due to increased survival. In contrast to the high mortality in SSA, where 50-90 percent of those with SCD may die in the first five years of life, it is currently claimed that over 94 percent of individuals born with SCD survive into adulthood in the US, France, and the UK. Patients may pass away young even before a diagnosis is identified in settings with limited resources or in nations where newborn screening is not yet a standard of treatment. Infections, severe anaemia (acute splenic sequestration, aplastic anaemia), and multi-organ failure are among the major reasons for death without an early diagnosis, education, preventative medicines such as penicillin prophylaxis, and routine surveillance. Therefore, it is crucial that countries, where SCD is a public health issue, give newborn and early infant diagnosis the priority it merits. Despite several assurances made by international organisations and politicians in front of the public, the majority of SSA nations are still unable to execute early newborn diagnosis. Only when this method is embraced by decision-makers across the continent and in India, where the majority of people with SCD are born and live, can screening’s advantages become important. Comprehensive care, which includes Hydroxycarbamide medication, preventative therapies such as antimalarials, and health promotion where appropriate, will improve results and quality of life concerning one’s health.


The most prevalent symptom of SCD is symptomatic anaemia, which is particularly prevalent in SCA (Homozygous S), which typically has the lowest haemoglobin level among double heterozygous forms. According to the phenotypic, steady-state haemoglobin levels for asymptomatic patients range from 60–80 g/L for homozygous S and /So forms to 100–110 g/L for double heterozygous SC and S+ forms. However, the rate at which a person’s steady-state haemoglobin level declines may result in hypoxia-related symptoms (aplastic crises) or a shock-like state (e.g., acute splenic sequestration).

Splenic Sequestration Crisis

The major job of the spleen is to get rid of sickled RBCs (sRBCs), which cause further hemolysis, and other damaged red blood cells. Slow blood flow via the spleen lowers oxygen tension and causes HbS to polymerize more quickly. The splenic vascular bed’s small capillaries cause RBC polymerization and the trapping of afflicted blood cells, which results in further hypoxia. The spleen grows as a result of a cycle of hypoxia, RBC polymerization, and reduced blood flow. For unknown reasons, this can happen rapidly, with blood collecting in the vascular bed and leading to shock and circulatory failure. Abdominal distension, abrupt weakness, increased thirst, tachycardia, and tachypnea could result from the spleen’s size expanding quickly. Splenic sequestration crisis is an emergency because, if untreated, it can cause circulatory failure that can result in death in 1-2 hours.

Treatment and Management

SCD has a variety of immediate and long-term side effects, necessitating a multidisciplinary treatment strategy involving many different medical specialities. The coordination of comprehensive SCD care in the UK is done by teams of experts in hemoglobinopathies. These teams are crucial in helping patients and their families learn about SCD. They also direct the use of disease-modifying treatments, access to psychological services, and social and welfare support. Additionally, they coordinate screening services like paediatric transcranial doppler (TCD) ultrasound monitoring, identifying iron overload or the development of alloantibodies in people receiving blood transfusions, and referring patients with serious organ complications who have an interest in SCD to specialists.

Severe combined immunodeficiency (SCID)

A potentially fatal illness and the first instance of the primary immunodeficiency disease is known as severe combined immunodeficiency (SCID) (PID). It consists of a diverse range of hereditary abnormalities and is distinguished by significant humoral and cellular immune system dysfunction brought on by a failure in T-cell development.

Neonates with SCID are healthy at birth and develop symptoms within the first few months of life from recurring infections brought on by different bacterial, viral, and fungal species.

Patients frequently show signs of pneumonia, sepsis, persistent oral candidiasis, chronic diarrhoea, and failure to thrive. The majority of infant deaths are caused by serious illnesses. Both autosomal recessive and X-linked recessive inheritance patterns are possible for SCID. Impacted lymphocyte subsets, it is categorised (T-cells, B-cells, NK-cells). Interleukin-2 receptor gamma chain (IL-2RG) gene mutation is the cause of 4, 5Xlinked SCID in 50% of cases. 4-6 Adenosine deaminase (ADA) gene mutation, which causes ADA deficiency, is the most frequent cause of autosomal recessive SCID and is present in 15-20% of all patients.

Allogenic hematopoietic stem cell transplantation is the preferred primary therapy for the majority of forms of SCID. Transplantation should be carried out before the onset of serious infection for the best results. Because adequate therapy must be started quickly, early diagnosis is crucial.1-6 Gene therapy has also been used to treat some types of SCID.

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