Medical Case Studies and Case Reports received 18 citations as per Google Scholar report
Received: 11-Nov-2022, Manuscript No. MCSCR-22-83849; Editor assigned: 14-Nov-2022, Pre QC No. MCSCR-22-83849 (PQ); Reviewed: 28-Nov-2022, QC No. MCSCR-22-83849; Revised: 05-Dec-2022, Manuscript No. MCSCR-22-83849 (R); Published: 12-Dec-2022, DOI: 10.15651/MCSCR.22.11.042
A rare genetic condition called Autoimmune Lymphoproliferative Syndrome (ALPS) causes the body's immune system cell count (lymphocytes) to become out of control. In ALPS, the lymph nodes, liver, and spleen store abnormally large amounts of white blood cells called lymphocytes. Anemia (low red blood cell count), thrombocytopenia (low platelet count), and neutropenia are other side effects of ALPS (low level of neutrophils, the most common type of white blood cell in humans). The risk of infection and bleeding can be increased by these issues. The creation of an excessively high number of lymphocytes is what defines ALPS (lymphoproliferation). Excess lymphocytes build up and expand the spleen, liver, and lymph nodes (lymphadenopathy), among other organs (splenomegaly).
ALPS can induce crippling symptoms and raise a person's risk of acquiring major medical disorders like cancer and autoimmune diseases. Targeting the genetic flaws in those with ALPS and associated illnesses, researchers are attempting to create safe and efficient treatments.
ALPS is also prone to autoimmune diseases. When the immune system disobeys and attacks the body's own tissues and organs, autoimmune illnesses result. The majority of ALPS related autoimmune diseases attack and harm the blood cells. For example, the immune system may attack platelets, white blood cells, or red blood cells. Less frequently, ALPS patients experience autoimmune diseases that affect other organs and tissues. These illnesses can cause nerve damage, kidney damage, liver damage, and autoimmune hepatitis (glomerulonephritis) (Guillain-Barre syndrome). ALPS can also experience skin issues like rashes or hives (urticaria).
The majority of ALPS patients inherit one faulty gene copy from one parent and one healthy gene copy from the other. Autosomal dominant inheritance is the term used for this. Not everyone who carries a defective copy of the gene develops ALPS. Parents may not be aware they carry the gene since 40% will not exhibit any symptoms.
New gene abnormalities can occasionally appear "out of the blue" in individuals without a family history of the condition. The genetic mutation is referred to as "sporadic" and may be transmitted to the following generation if it happens during conception (in the eggs or sperm). A gene mutation is referred to as a "somatal" variant if it appears later in the embryo's development and solely affects blood cells. Somatic variants cannot be passed on to subsequent generations. It is rare for ALPS to be inherited in an autosomal recessive form, meaning that both parents carry the mutated gene but do not experience any symptoms.
Different patterns of symptoms and indications might be present with ALPS. Childhood is when lymphoproliferation is most frequently noticed at first. In affected people, swelling of the lymph nodes and spleen is common. Typically, autoimmune diseases appear years or even decades after the onset of hemolytic anaemia and thrombocytopenia, also known as Evans syndrome. Compared to the general population, those who have this type of ALPS typically live close to normal lives but are at significantly higher risk of getting lymphoma, a cancer of the immune system.
Lymphoproliferation, lymphadenopathy, splenomegaly, and low blood counts are among the signs and symptoms that some people have in common with ALPS. However, the precise pattern of these symptoms or the underlying genetic aetiology may vary. Whether these non-classical variants should be classified as an additional condition or as ALPS varies among researchers.
Chronic lymphadenopathy and/or splenomegaly in a kid who is otherwise healthy is the first clinical sign of ALPS, which is frequently identified by the physician in a wellbaby clinic. Similar to the age at which lymphocyte repertoires begin to expand in children, symptomatic multilineage cytopenias that are also chronic and refractory are typically at their worst in early childhood. However, by the time they reach adolescence and young adulthood, these conditions have a tendency to get better. Many ALPS patients may have periods of tiredness, pallor, and icterus linked to hemolytic anemia; spontaneous bruising and mucocutaneous haemorrhages linked to thrombocytopenia; or bacterial infections linked to neutropenia.
On their long-term follow-up over many years, some patients with ALPS are showing signs of developing multiple autoimmune as well as infiltrative lymphoproliferative disorders affecting various organ systems, such as uveitis, hepatitis, glomerulonephritis, infiltrative pulmonary lesions, and encephalitis and myelitis (manifesting aseptic meningitis).
The presence of polyclonal hypergammaglobulinemia and cytopenias due to autoimmune destruction or splenic sequestration are the most frequent test results. Due to a number of reasons, including hypersplenism, autoimmune disease, and iron deficiency, anaemia is almost universal.
In patients with ALPS, eosinophilia and monocytosis are also common findings, although the precise pathophysiologic mechanism underlying these is unknown. The clinical and laboratory features of children with generalised adenopathy, splenomegaly, and autoimmune multilineage cytopenias overlap with those of other childhood hematologic disorders, such as lymphoma, hemophagocytic lymphohistiocytosis, hereditary spherocytosis, Evans syndrome, and Rosai- Dorfman disease, making a diagnosis difficult.
Currently, the presence of two necessary and six additional criteria is required for the diagnosis of ALPS. Chronic lymphadenopathy, splenomegaly, and increased circulating TCR-positive DNT cells are necessary requirements. To further divide additional criteria, primary and secondary categories are used. The two main extra requirements are a defective lymphocyte apoptosis assay and the existence of pathogenic mutations in genes involved in the FAS pathway. Elevated circulating biomarkers, distinctive histology, and a family history consistent with ALPS make up the secondary extra criteria.
A patient must satisfy both the essential criteria and one of the two main supplementary criteria in order to receive a conclusive ALPS diagnosis. If the required criteria and any one of the secondary extra criteria are met, an ALPS diagnosis is considered probable. Patients with probable ALPS should get the same care and monitoring as those with a confirmed diagnosis, but treating doctors are encouraged to undertake genetic or apoptotic assay based diagnostic workups whenever practical.