The patient was an infant girl born after thirty-six weeks’ gestation. A low birth weight for gestational age and small neonatal size with microcephaly were noted. The skin was covered with numerous small hemorrhages (petechiae) and appeared yellow (was jaundiced), indicating liver disease. The abdomen was markedly distended because of extreme enlargement of both the liver and the spleen (FIGURE 4-9). A CT scan of the head disclosed multiple defects, with enlargement of the fluid-filled spaces (ventricles) of the brain and abnormal deposits of calcium. The infant was moderately anemic, and the platelet count was reduced, which accounted for the widespread hemorrhages in the skin. Elevation of liver-specific enzymes in the infant’s blood suggested serious liver disease. The infant was considered to be seriously ill as a result of a prenatal infection acquired from the mother. Diagnostic possibilities considered were congenital rubella, cytomegalic inclusion disease, systemic herpes virus infection, or toxoplasmosis. The infant died from widespread infection about five hours after examination before further diagnostic studies could be undertaken. The autopsy revealed the infection was caused by the cytomegalovirus. Pneumonia was detected, and characteristic cytomegalovirus inclusions were found in the lung. The diagnosis of congenital CMV infection was confirmed by additional laboratory tests (FIGURE 4-10).
FIGURE 4-9
FIGURE 4-10
Discussion
Cytomegalovirus infection (CMV) is the most common congenital infection, infecting between 0.6 and 1.0 percent of all births in the developing and developed world. CMV is a herpes virus that usually leads to asymptomatic disease in adults and children with normal immune systems. In developing countries, nearly 100 percent of people have been infected and have acquired antibodies to the virus (are seropositive) early in life. The number of seropositive people in developed countries reaches only about 50 percent in young adults. Although the risk of congenital CMV is greatest when the mother is first infected during pregnancy (and in particular during the first half), having antibodies to the virus does not rule out potential infection in utero. In a population in which more than 95 percent of pregnant women were seropositive, 1 percent of neonates were infected at birth and almost all were born of mothers who were seropositive prior to pregnancy. Only 10 percent of CMV-infected neonates show signs of disease at birth, although this group is almost always born to mothers who have had their first CMV infection during pregnancy. Such neonates are most frequently severely affected (as described in Case 4-1). The 90 percent of CMV-infected neonates who do not show disease at birth have a 10 to 20 percent risk of developing sequelae during childhood; most commonly hearing loss. Antiviral therapy may be considered in children with severe disease, but this is associated with significant side effects.
Etiology and Pathogenesis
The etiology is CMV infection in utero followed by multiorgan damage as a result of viral infection.
Questions
1. The physician attending the child considered a limited number of diseases to explain the symptoms observed. Why were these particular agents considered?
2. A definitive diagnosis was made at autopsy. How was this achieved?
3. Assume the child had survived. What other laboratory procedures could have been undertaken to establish a diagnosis of CMV?