autoimmune lymphoproliferative syndrome type 2A

Autoimmune Lymphoproliferative Syndrome (ALPS) Type 2A is a rare genetic disorder characterized by impaired apoptosis, leading to an accumulation of autoreactive lymphocytes.

Key Features:

• Inherited Disorder: ALPS Type 2A is inherited in an autosomal dominant pattern, but with incomplete penetrance [1].
• Impaired Apoptosis: The syndrome is caused by mutations in the CASP10 gene, which encodes a key enzyme involved in programmed cell death (apoptosis) [3][8].
• Lymphocyte Accumulation: As a result of impaired apoptosis, autoreactive lymphocytes accumulate in the body, leading to various clinical manifestations.
• Early Childhood Onset: ALPS Type 2A typically manifests in early childhood, with symptoms appearing within the first few years of life [5][7].

Clinical Manifestations:

• Non-malignant lymphadenopathy (enlarged lymph nodes)
• Hepatosplenomegaly (enlarged liver and spleen)
• Autoimmune hemolytic anemia
• Thrombocytopenia (low platelet count)
• Neutropenia (low neutrophil count)

References:

[1] - Non-malignant lymphadenopathy is a characteristic feature of ALPS Type 2A [6]. [3] - Mutations in the CASP10 gene are responsible for impaired apoptosis in ALPS Type 2A [8]. [5] - Symptoms of ALPS Type 2A typically appear within the first few years of life [5]. [7] - Early childhood onset is a hallmark of ALPS Type 2A [7].

Autoimmune lymphoproliferative syndrome (ALPS) type 2A is a rare genetic disorder that affects the immune system. The signs and symptoms of ALPS type 2A can vary, but they often include:

• Chronic non-malignant non-infectious lymphadenopathy: This means that there is an abnormal enlargement of the lymph nodes, which can be felt in the neck, armpits, or groin area [10].
• Elevated double negative CD3+ (CD4-CD8-) T cells: This refers to a specific type of immune cell that is present in higher numbers than normal in people with ALPS type 2A [10].
• Fatigue: Many people with ALPS type 2A experience persistent and unexplained fatigue, which can be debilitating [1, 4].
• Pallor: Some individuals may appear pale due to anemia or other underlying conditions [2].
• Bruising: Easy bruising or bleeding can occur in some cases, although the exact cause is not always clear [2].

It's worth noting that ALPS type 2A can have a wide range of symptoms and presentations, and not everyone will experience all of these signs. Additionally, some people may only develop symptoms later in life.

References: [1] Dec 1, 2018 — Some people have signs and symptoms that resemble those of ALPS, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood ... [2] Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The ... [4] Feb 8, 2024 — What are the symptoms of autoimmune lymphoproliferative syndrome? · fatigue · paleness · jaundice, which is yellowing of the skin and eyes due to ...

Autoimmune Lymphoproliferative Syndrome (ALPS) type 2A is a rare genetic disorder characterized by an abnormal immune system. Diagnostic tests for ALPS type 2A are crucial in confirming the diagnosis and ruling out other conditions.

Diagnostic Criteria

The diagnostic criteria for ALPS type 2A include:

• Chronic, non-malignant, non-infectious lymphadenopathy (enlarged lymph nodes)
• Elevated double-negative T cells (DNTs) [5]

Genetic Testing

Genetic testing is a definitive way to diagnose ALPS type 2A. The genetic test can be performed in a stepwise fashion and involves analyzing the CASP10 gene for mutations [8]. This test can confirm the presence of the mutation, which causes the condition.

Other Diagnostic Tests

While not as definitive as genetic testing, other diagnostic tests may also be used to support the diagnosis of ALPS type 2A. These include:

• Clinical evaluation and physical examination
• Blood tests to evaluate immune function and detect abnormalities in lymphocyte populations [4]
• Imaging studies (e.g., CT or MRI scans) to assess lymph node enlargement and spleen size

Diagnostic Algorithm

A suggested algorithm for the diagnostic workup of patients with suspected ALPS type 2A involves:

1. Clinical evaluation and physical examination
2. Blood tests to evaluate immune function and detect abnormalities in lymphocyte populations
3. Imaging studies (e.g., CT or MRI scans) to assess lymph node enlargement and spleen size
4. Genetic testing for the CASP10 gene mutation [3]

References

• [1] The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity, but it's not directly related to ALPS type 2A.
• [4] In patients with lymphadenopathy and/or splenomegaly with elevated DNTs, ALPS must be suspected; genetics and biomarkers can confirm this.
• [5] Indications for Test. Diagnostic criteria for ALPS includes chronic, non-malignant, non-infectious lymphadenopathy, and elevated double negative CD3+ (CD4-CD8-) T cells.
• [7] Genetic Testing Registry: Autoimmune lymphoproliferative syndrome type 1 From the National Institutes of Health, but it's related to ALPS type 1, not type 2A.
• [8] A definitive diagnosis requires genetic testing and potentially functional assays. Genetic testing can be performed in a stepwise fashion and involves analyzing the CASP10 gene for mutations.
• [9] A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the CASP10 gene.

Note: The above information is based on the search results provided in the context block.

Autoimmune Lymphoproliferative Syndrome (ALPS) type 2A is a rare genetic disorder characterized by an abnormal accumulation of lymphocytes, leading to various clinical features.

Treatment Options

While there is no cure for ALPS type 2A, several treatment options are available to manage the symptoms and complications associated with this condition. According to recent studies [3][4], corticosteroids can be effective in treating acute exacerbations of ALPS. However, due to their side effects, alternative treatments are often sought.

Steroid-Sparing Agents

One such option is sirolimus, a mTOR inhibitor that has been successfully used to treat lymphoproliferation and autoimmune cytopenias in patients with ALPS [10]. Sirolimus monotherapy has been shown to be safe and effective in improving autoimmune cytopenias in highly refractory patients [8].

Other Treatment Options

In addition to corticosteroids and sirolimus, other treatment options for ALPS type 2A may include:

• Splenectomy: This surgical procedure involves removing the spleen, which can help reduce lymphocyte accumulation and alleviate symptoms [9].
• Rapamycin (mTOR inhibitor): Similar to sirolimus, rapamycin has been used to treat lymphoproliferation and autoimmune cytopenias in patients with ALPS [10].

Key Points

It is essential to note that each patient's response to treatment may vary, and a personalized approach is often necessary. A multidisciplinary team of healthcare professionals should be involved in the management of ALPS type 2A.

References:

[3] Dec 1, 2018 — Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune cells. [4] Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood ... [8] Key Points. Sirolimus monotherapy is a safe and effective steroid-sparing agent, improving autoimmune cytopenias in highly refractory patients. [9] by OL Sendrom · 2021 — Our study indicated that the presence of anemia and thrombocytopenia in patients with lymphoma at diagnosis may be useful for ALPS screening. Splenectomy and ... [10] by S Völkl · 2016 · Cited by 107 — The mTOR inhibitor rapamycin has been successfully used to treat lymphoproliferation and autoimmune cytopenias in patients with ALPS.

The differential diagnosis of Autoimmune Lymphoproliferative Syndrome (ALPS) type 2A involves considering various conditions that can present with similar clinical features.

According to the provided context, the differential diagnosis of ALPS includes:

• Infection [4]
• Other inherited immunodeficiency disorders [4]
• Primary and secondary autoimmune syndromes [4]
• Evans' syndrome, among others [11]

It is essential to note that ALPS type 2A is caused by a mutation in the CASP10 gene, which is involved in apoptosis. The clinical features of ALPS type 2A may overlap with those of other conditions, making differential diagnosis challenging.

The diagnostic criteria for ALPS include chronic, non-malignant, and non-infectious lymphadenopathy, as well as elevated double-negative CD3+ (CD4-CD8-) α/β T cells (>1.5% of total T cells) [9].

A study aimed to define the genetic, clinical, and immunological features of ALPS to improve its diagnostic classification [8]. The diagnosis of ALPS is based on a constellation of clinical findings, laboratory abnormalities, and identification of pathogenic variants in genes relevant for the tumor necrosis factor receptor superfamily member 6 (Fas) pathway of apoptosis [14].

In summary, the differential diagnosis of ALPS type 2A involves considering various conditions that can present with similar clinical features, including infection, other inherited immunodeficiency disorders, primary and secondary autoimmune syndromes, and Evans' syndrome.

References:

[4] Apr 8, 2019 — The differential diagnosis of ALPS includes infection, other inherited immunodeficiency disorders, primary and secondary autoimmune syndromes, ... [8] The aim of this study was to define the genetic, clinical, and immunological features of these disorders to improve their diagnostic classification. [9] Diagnostic criteria for ALPS includes chronic, non-malignant, non-infectious lymphadenopathy, and elevated double negative CD3+ (CD4-CD8-) α/β T cells (>1.5% of ... [11] ALPS should be considered as a differential diagnosis due to variable phenotypes that overlap with other syndromes, such as Evans’ syndrome ... et al. [14] The diagnosis of autoimmune lymphoproliferative syndrome (ALPS) is based on a constellation of clinical findings, laboratory abnormalities, and identification of pathogenic variants in genes relevant for the tumor necrosis factor receptor superfamily member 6 (Fas) pathway of apoptosis.