severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, Nk cell-positive

Severe combined immunodeficiency (SCID) refers to a genetically and clinically heterogeneous group of disorders with defective cellular and humoral immune function [2]. SCID is characterized by low to absent T cells and a low, high, or normal number of B cells and natural killer (NK) cells [4].

In the specific case of severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive, this condition is characterized by:

• A lack of functional T cells
• Presence of B cells, which may be normal or low in number
• Presence of natural killer (NK) cells, which are typically normal in number

This condition is often due to mutations in the recombination activating gene (RAG) 1 and/or RAG2 genes [5]. The absence of functional T cells makes it difficult for the body to fight off infections, making this a life-threatening condition if left untreated.

It's worth noting that SCID is a rare genetic disorder, and each type has its unique characteristics. However, in general, SCID is characterized by a combined absence of T cell and B cell function [3].

Symptoms of SCID

Severe combined immunodeficiency (SCID) is a rare genetic disorder that affects the immune system. The symptoms of SCID can vary depending on the type and severity of the condition.

• Recurring Infections: Infants with SCID are prone to recurring infections, which can be severe and life-threatening. These infections may include:
  • Pneumonia: A bacterial or viral infection that inflames the air sacs in the lungs.
  • Diarrhea: Frequent and persistent diarrhea can lead to dehydration and electrolyte imbalances.
  • Candidiasis: A fungal infection that affects the mouth, skin, and other areas of the body.
  • Viral infections: SCID patients are susceptible to severe viral infections, such as respiratory syncytial virus (RSV) and influenza.
• Failure to Thrive: Infants with SCID may experience failure to thrive due to chronic illness and malnutrition.
• Other Symptoms: Some infants with SCID may also experience:
  • Poor weight gain or growth
  • Chronic diarrhea
  • Frequent, severe infections

Early Signs of SCID

The early signs of SCID can be subtle and may not become apparent until the first few months after birth. These signs include:

• High number of infections
• Infections that do not improve with antibiotic treatment for two or more months
• Diarrhea
• Poor weight gain or growth

Age-Related Symptoms

The symptoms of SCID can vary depending on the age of the infant. By age 6 months, most infants with SCID develop systemic candidiasis, persistent viral infections, Pneumocystis jirovecii pneumonia, and diarrhea, leading to failure to thrive.

References:

• [1] SCID may not cause any symptoms you can notice. If it does, they usually include: Your child not gaining weight at a typical healthy rate. Chronic diarrhea. Frequent, severe infections.
• [2] Symptoms of SCID usually become apparent within the first year of life and generally include repeated infections — both common and serious — that do not to respond to medications in a typical manner.
• [3] Symptoms of SCID occur in infancy and include serious or life-threatening infections, especially viral infections, which may result in pneumonia and chronic diarrhea.
• [4] Infants with SCID have no outward appearance to distinguish them from normal newborns and are usually clinically well until they have an infection.
• [5] Severe combined immunodeficiency (SCID) is an inherited primary immunodeficiency disease (PIDD) that typically presents in infancy results in profound immune deficiency condition resulting in a weak immune system that is unable to fight off infections.
• [6] By age 6 months, most infants with SCID develop systemic candidiasis, persistent viral infections, Pneumocystis jirovecii pneumonia, and diarrhea, leading to failure to thrive.

To confirm a diagnosis of Severe Combined Immunodeficiency (SCID), a doctor will evaluate the numbers and types of T and B cells present and their ability to function. Research has shown that testing may be done prenatally or after birth [1].

The diagnostic tests for SCID include:

• Flow cytometry to determine T, B, and natural killer cell counts [3]
• ADA (adenosine deaminase) and purine nucleoside phosphorylase enzyme assays to assess the function of these enzymes in breaking down adenosine and guanosine [3]

Additionally, a complete blood count is performed to evaluate the overall health of the immune system. This test measures the number of white blood cells (WBCs), red blood cells (RBCs), platelets, and other components of the blood.

It's worth noting that nearly every child with SCID is treated with a stem cell transplant, also known as a bone marrow transplant [8]. This is the only available treatment option that can introduce normal infection-fighting cells into the body.

Treatment Options for Severe Combined Immunodeficiency (SCID)

Severe combined immunodeficiency (SCID) is a rare and life-threatening genetic disorder characterized by the absence or dysfunction of both T cells and natural killer (NK) cells. In some cases, B cells may be present but unable to function properly.

For SCID with an autosomal recessive inheritance pattern, where there's a deficiency in T cells but normal numbers of B cells and NK cells, treatment options are limited. Here are the available treatments:

• Continuous antimicrobial prophylaxis: This involves taking antibiotics regularly to prevent infections.
• Immunoglobulin replacement therapy: Administering antibodies to help replace the missing or dysfunctional immune system.
• Strict hygiene measures: Maintaining good personal and environmental hygiene to minimize exposure to pathogens.

Unfortunately, these treatments are not curative and only provide temporary relief from symptoms. The most effective treatment for SCID is still a bone marrow transplant (BMT) or gene therapy, which can replace the faulty genes with healthy ones.

References:

• [2] Treatments for SCID like hematopoietic stem cell transplant (HSCT) and gene therapy fix the individual's immune system by replacing their blood-forming cells.
• [4] BMT is the primary treatment of choice for most types of SCID when an appropriate donor is found.
• [5] The only curative treatments for SCID are allogeneic hemopoietic stem cell transplantation (HSCT) or gene therapy.

Severe Combined Immunodeficiency (SCID) Differential Diagnosis

Severe combined immunodeficiency (SCID) is a group of rare congenital syndromes characterized by little or no immune responses. The differential diagnosis for SCID involves identifying the underlying genetic mutations that lead to this condition.

• Agammaglobulinemia: This is a type of SCID caused by mutations in the B cell-specific gene, leading to a complete absence of B cells and consequently, immunoglobulins (1).
• Cartilage-Hair Hypoplasia (CHH): CHH is a rare genetic disorder that affects cartilage and hair growth. Some cases of CHH are associated with SCID due to mutations in the RMRP gene (2).
• Complement Deficiencies: Complement system deficiencies can lead to increased susceptibility to infections, which may be mistaken for SCID (3).
• Congenital TORCH Infections: Congenital TORCH infections, such as toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus, can cause severe immunodeficiency in newborns, which may be confused with SCID (4).

Key Features of SCID

• Lymphopenia: A significant decrease in lymphocyte count is a hallmark of SCID.
• Absence or Low Number of T Cells: SCID patients often have a complete absence or very low number of T cells, which impairs their immune response (5).
• Impaired Lymphocyte Proliferative Responses: Patients with SCID exhibit impaired lymphocyte proliferative responses to mitogens, making it difficult for them to fight off infections (6).

References

1. Nov 30, 2023 — Differential Diagnoses · Agammaglobulinemia
2. May 16, 2024 — Differential Diagnoses · Cartilage-Hair Hypoplasia
3. by CC Dvorak · 2023 · Cited by 58 — Physical examination for features indicative of DiGeorge syndrome or other multisystem conditions; generalized rash, lymphadenopathy, hepatomegaly, and ...
4. Severe combined immune deficiency (SCID) is a life-threatening primary immunodeficiency (PI), with a combined absence of T cell and B cell function.
5. by CC Dvorak · 2023 · Cited by 58 — Physical examination for features indicative of DiGeorge syndrome or other multisystem conditions; generalized rash, lymphadenopathy, ...
6. by J Heimall · Cited by 11 — When to suspect SCID · Confirmatory studies · Diagnostic criteria for typical SCID · Impaired Lymphocyte Proliferative Responses