Chapter 50

### INTRODUCTION

As detailed in chapter 49, host defense mechanisms against pathogens are defective in the newborn as a result of immature immunity. Preterm infants are particularly vulnerable to infections associated with prematurity-related complications and medical interventions. The recognition of inborn errors of immunity and differentiation from functional immaturity of the immune system pose a diagnostic challenge. An organized clinical approach is essential to facilitate early diagnosis, which has a significant impact on prognosis and survival.

To date, more than 150 monogenic primary immunodeficiency disorders (PIDs) have been described.1 They can be classified into (1) combined T- and B-cell immunodeficiencies, (2) predominantly antibody deficiencies, (3) immune dysregulatory syndromes, (4) phagocytic disorders, (5) defects in innate immunity, (6) diseases of immune dysregulation, (7) complement deficiencies, and (8) other well-defined disorders, such as Wiskott-Aldrich syndrome (WAS) and DNA repair defects. Among them, combined T- and B-cell deficiencies constitute the most clinically important group of disorders in neonates and infants. The lack of cell-mediated immunity results in susceptibility to opportunistic infections, which is the principle manifestation leading to diagnosis in most infants with severe combined immunodeficiency (SCID). In addition, defective T-cell homeostasis may lead to immune dysregulation and lymphoproliferation, which are less commonly encountered in the neonatal period.

### EPIDEMIOLOGY

Primary immunodeficiency disorders are rare disorders. SCID is estimated to occur in 1:50,000 to 1:100,000 live births, but the exact incidence is unknown as some affected infants might have died before a diagnosis could be made.2 In addition, atypical SCID caused by hypomorphic mutations may be underdiagnosed. The implementation of newborn screening (NBS) for SCID is expected to provide epidemiological data on the true incidence rate.

The spectrum of immunological phenotypes and genetic etiology vary with ethnic background and consanguinity rate of the population. In the United States, interleukin (IL) 2 receptor γ chain (γc) deficiency of TB+ immunophenotype inherited in an X-linked manner accounts for 45%–50% of SCID.2 However, TBSCID of autosomal recessive (AR) inheritance predominates in the Athabascan-speaking Navajo and Apache native Americans because of the high frequency of DCLRE1C (Artemis) founder mutation (2.1%), giving rise to an incidence as high as 1:2000 live births in these ethnic groups.3 AR-SCIDs are also more common in populations with a high prevalence of consanguineous marriage, such as North Africa and the Middle East.4, 5, and 6

Other types of T-cell disorders presenting in the neonatal and infancy period, such as WAS and familial hemophagocytic lymphohistiocytosis, are much rarer, and the incidence varies from 1:100,000 to 1:1,000,000.7, 8

### PATHOPHYSIOLOGY

The immune response is a complex host defense network that functions to protect the body against pathogens, recognize self- and non-self-antigens, sense DNA damage, and eliminate malignant clones. To achieve these tasks, the system requires a functional repertoire consisting of ...

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

## Subscription Options

### AccessPediatrics Full Site: One-Year Subscription

Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.