Autoimmune Lymphoproliferative Syndrome (ALPS)
Description
Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disorder that affects the immune system. Individuals with ALPS have a deficiency in a protein called Fas, which plays a crucial role in regulating the death of immune cells. This deficiency leads to an accumulation of abnormal lymphocytes, increasing the risk of autoimmune diseases and lymphoma. This blog will provide a comprehensive overview of ALPS, including its causes, symptoms, diagnosis, and management.
Genes Involved
ALPS is caused by mutations in genes involved in the Fas-mediated apoptotic pathway. The most commonly affected gene is FAS, which encodes the Fas protein. Other genes that can be mutated in ALPS include:
- CASP10
- CASP8
- FADD
- TNFRSF6
- TNFRSF10B
Recognizing the Signs and Symptoms
ALPS can present with a range of symptoms, including:
- Enlarged lymph nodes: Swollen lymph nodes, particularly in the neck, armpits, and groin, are a common symptom.
- Splenomegaly: An enlarged spleen is another frequent finding.
- Autoimmune diseases: People with ALPS are at increased risk of developing autoimmune disorders such as autoimmune hemolytic anemia, thrombocytopenia, and autoimmune neutropenia.
- Lymphoma: A higher risk of developing lymphoma, a type of cancer affecting the lymphatic system, is associated with ALPS.
- Recurrent infections: Due to the impaired immune system, individuals with ALPS may experience frequent infections.
- Fatigue and weakness: Persistent tiredness and lack of energy can occur due to the ongoing immune system activation.
- Fever: Recurrent episodes of fever can be a sign of ALPS.
- Hepatitis: Inflammation of the liver, known as hepatitis, may occur in some cases.
Causes
ALPS is a genetic disorder caused by mutations in specific genes involved in the regulation of apoptosis, the process of programmed cell death. These mutations disrupt the normal function of the Fas protein, which plays a vital role in eliminating excess or abnormal immune cells. The deficiency in Fas protein leads to an accumulation of lymphocytes, which can trigger autoimmune responses and increase the risk of lymphoma.
Inheritance/recurrence risk
ALPS is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. If both parents carry the mutated gene, there is a 25% chance with each pregnancy that their child will inherit two copies and develop ALPS. However, if only one parent carries the mutated gene, their children have a 50% chance of inheriting the mutated gene and becoming carriers. Carriers are typically asymptomatic but can pass the gene on to their offspring.
