SNP Shot: Genomic Insights

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic condition where the body's immune system can't properly control the number of lymphocytes (immune cells). A key feature of ALPS is lymphoproliferation, an overproduction of lymphocytes. This excess of lymphocytes leads to enlarged lymph nodes (lymphadenopathy), an enlarged liver (hepatomegaly), and an enlarged spleen (splenomegaly).

Autoimmune problems are frequently seen in ALPS. These occur when the immune system mistakenly attacks the body's own healthy tissues and organs. Often, in ALPS, this autoimmune attack targets blood cells. For instance, the immune system might attack red blood cells (resulting in autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune issues affecting other organs, like the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), or nerves (Guillain-Barre syndrome), can occur. Skin issues, such as rashes or hives (urticaria), are also possible in individuals with ALPS.

The symptoms of ALPS can vary. Lymphoproliferation typically becomes noticeable in childhood. Enlarged lymph nodes and an enlarged spleen are common. Autoimmune disorders usually develop later, often as a combination of hemolytic anemia and thrombocytopenia, known as Evans syndrome. People with this classic presentation of ALPS usually have a near-normal life expectancy, but their risk of developing lymphoma (cancer of the immune system cells) is significantly higher compared to the general population.

Some individuals exhibit ALPS-like symptoms, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood counts. However, the specific combination of these symptoms or the underlying genetic cause may differ. There is debate among researchers about whether these "non-classic" cases should be classified as ALPS or a separate condition.

Inheritance:

In most people with ALPS, particularly those with FAS gene mutations, the condition follows an autosomal dominant inheritance pattern. This means that only one copy of a mutated gene in each cell is enough to cause the disorder. Usually, the affected person inherits the mutated gene from one parent who also has the condition. In other autosomal dominant cases, the mutation arises spontaneously (de novo) during early embryonic development in individuals with no family history of ALPS. In a minority of cases, including some with FAS gene mutations, ALPS is inherited in an autosomal recessive pattern. This requires both copies of the gene in each cell to be mutated. The parents of someone with an autosomal recessive condition each carry one copy of the mutated gene, but they typically don't show symptoms of ALPS. ALPS can also result from a somatic mutation, a genetic change in lymphocytes that occurs during a person's lifetime and is not inherited.