Unusually difficult clinical presentation of an infant suffering from congenital cytomegalovirus (CMV) infection combined with alpha 1-antitrypsin (A1AT) deficiency

Abstract

Congenital Cytomegalovirus (CMV) infection and alpha 1-antitrypsin (A1AT) deficiency are separately well described entities, but their simultaneous occurrence can pose a special challenge to a clinician, especially dealing with optimal diagnostic as well as therapeutic approach. Congenital CMV infection is the most common vertically transmitted infection in developed countries. In 85–95% of newborns it runs asymptomatic, while in others it is presented with jaundice, petechias, hepatosplenomegaly and central nervous system damage. A1AT deficiency is on the other hand, the most common genetic liver disease in children, and the clinical spectrum varies from the accidentally detected increased levels of transaminases through to the severe infant cholestasis that can progress to cirrhosis. The following case report describes a two-month old male with severe clinical presentation of congenital CMV infection probably exacerbated due to A1AT deficiency comorbidity. The clinical manifestations and unusually difficult clinical signs this infant presented lead to assumption that the additional liver damage exists. Extensive laboratory analyses were performed, including PCR for CMV DNA, A1AT serum concentration, A1AT genotyping, followed and confirmed with phenotyping. Patient was treated parenteral with ganciclovir, what continued with oral valganciclovir and supportive therapy. Intensive and thorough supportive treatment of the infant resulted in satisfactory progress and excellent outcome. Patient was followed-up till the age of 18 months. The presented case provides excellent example about successful overcoming obstacles in differential diagnosis of A1AT in neonates and infants. Medical charts analysis was the methodology used in making this report.

Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Approaches and Future Directions

“…Although A1ATD is typically diagnosed in patients that are homozygous for the mutation, Perlmutter and colleagues found that a significant portion of patients transplanted for A1ATD were actually heterozygous for the mutation (mostly PiMZ), but found to have another “second hit” insult that could have caused or contributed to more rapid progression of end-stage liver disease [ 25 , 26 ]. These risk factors include infections (CMV and hepatitis B and C), genetic disorders (cystic fibrosis), and other co-morbidities (obesity, alcoholism) [ 25 , 27 , 28 ]. Environmental factors such as cigarette smoking can propagate ongoing lung injury [ 29 – 32 ].…”

A Challenging Case of Severe Infantile Cholestasis in Alpha-1 Antitrypsin Deficiency

“…There have been isolated reports of rapid deterioration and acute liver failure in infants with A1ATD and concomitant infections, such as congenital cytomegalovirus viremia, which was ruled out in our patient. 13,14 Since she required early liver transplantation, we were unable to send whole-exome sequencing, which may have revealed a ''second hit.'' Nevertheless, her post-transplant course has thus far been reassuring and does not suggest coexisting systemic disease.…”