Screening

Population-based screening of newborns for severe combined immunodeficiency (SCID) involves the quantification of blood levels of T-cell–receptor excision circles (TRECs), which are DNA by-products of T-cell–receptor rearrangement that indicate thymic production of naive T cells.1

Inadequate TREC levels prompt immunologic investigation to diagnose SCID before infections occur, which permits the timely initiation of therapy; therapy usually involves allogeneic hematopoietic stem-cell transplantation from a healthy donor.2 In addition to enhancing the efficacy of treatment,2,3 newborn screening can reveal previously unknown causes of T-cell lymphopenia.1,4-7

Severe Combined Immune Deficiency (SCID) leads to life-threatening infections unless the immune system can be restored through a bone marrow transplant, enzyme replacement or gene therapy. Infants with SCID who lack a family history have been diagnosed in the past only after developing serious infections. Early identification of SCID through screening of all newborns can make possible life-saving intervention before infections occur. Currently, several states have adopted the T-cell receptor excision circle (TREC) assay as part of their routine newborn screening programs. TREC screening has identified infants with most forms of SCID and also some infants with very low T-lymphocytes due to other conditions.

IDF SCID Newborn Screening Campaign
Currently, many states have added SCID to their newborn screening panel, and IDF’s goal is to have all states add SCID. You can learn more about the IDF SCID Newborn Screening Campaign and become a successful advocate. Click here for more information.

IDF SCID Initiative
The IDF SCID Initiative, comprised of community members with specialized interest and knowledge specific of SCID, is dedicated to education, awareness, and diagnosis the disease. Click here for more information.

The Story of David
David Vetter, affectionately known as the boy in the bubble, was born with SCID. At the time of his birth in 1971, a bone marrow transplant from an exact matched donor was the only cure for SCID, but there was no match available in David’s family. For 12 years, David captured the world’s attention as he lived in protected environments to maintain relatively germ-free surroundings at Texas Children’s Hospital. Click here to read more about David.

 

Symptoms

Signs

Laboaratory Tests

Whole-exome sequencing in persons with rare disorders of immunity has led to the identification of genes that had not previously been associated with SCID.5

However, definitively identifying a causative variant among candidate variants can be challenging. Accordingly, efficient functional tests to study mechanisms of pathogenesis are essential.

Zebrafish are useful for understanding human genetics and immunity8-10 because of both the ease with which they can be genetically manipulated and their fidelity in modeling human diseases.11-13

We used whole-exome sequencing in conjunction with functional analysis of a candidate gene in human hematopoietic stem cells and in zebrafish to determine the cause of a unique case of SCID that was found through newborn screening.

The patient had “leaky” SCID (i.e., a form of SCID in which a minimal degree of immune function is preserved) and developmental abnormalities, which we traced to a BCL11B variant.

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Population-based screening of newborns for severe combined immunodeficiency (SCID) involves the quantification of blood levels of T-cell–receptor excision circles (TRECs), which are DNA by-products of T-cell–receptor rearrangement that indicate thymic production of naive T cells.1 Inadequate TREC levels prompt immunologic investigation to diagnose SCID before infections occur, which permits the timely initiation of therapy; therapy usually involves allogeneic hematopoietic stem-cell transplantation from a healthy donor.2 In addition to enhancing the efficacy of treatment,2,3 newborn screening can reveal previously unknown causes of T-cell lymphopenia.1,4-7

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Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.

 

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Question 1 of 1

A 42-year-old African-American man has been diagnosed with hypertension for the past 10 years and treated with medication. One morning, he is found unresponsive by his wife. He is taken to the emergency department and pronounced dead by the physician. An autopsy revealed cardiac hypertrophy and a narrowing of the aorta just distal to the ligamentum arteriosum, with dilation of the intercostal artery's ostia. How could the death have possibly been prevented?

Answer

 

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