# Chromosomal Integration of HHV-6 in a Preterm Neonate: A Rare Case of Hyperleukocytosis and Clinical Implications

## TL;DR

A preterm neonate with high white blood cell count was found to have chromosomally integrated HHV-6, a rare condition that can mimic leukemia.

## Contribution

This case highlights ciHHV-6 as a rare cause of neonatal hyperleukocytosis and emphasizes the diagnostic value of whole-blood PCR.

## Key findings

- A preterm neonate presented with hyperleukocytosis and was diagnosed with chromosomally integrated HHV-6.
- Whole-blood quantitative PCR confirmed ciHHV-6 rather than active infection, avoiding unnecessary antiviral treatment.
- The neonate remained asymptomatic, emphasizing the importance of accurate diagnosis in neonatal hyperleukocytosis.

## Abstract

Leukocytosis in neonates can occur because of infectious, inflammatory, malignant, or physiological processes. Hyperleukocytosis is defined as a total leukocyte count (TLC) exceeding 100,000 per mm3, warranting immediate evaluation. Neonates with hyperleukocytosis are at risk of leukostasis and the associated severe complications, including respiratory distress, myocardial ischemia, hyperuricemia, acute renal failure, infarction, and hemorrhage. Differentiating leukemia and leukemoid reactions in neonates presenting with elevated TLC is challenging but critical. We present a unique case of a preterm male neonate with hyperleukocytosis, initially suspected to have an underlying malignancy. The neonate’s clinical course was complicated by respiratory distress syndrome and anemia of prematurity, necessitating neonatal intensive care unit management. Further investigation revealed high human herpesvirus 6 (HHV-6) DNA levels in the whole blood, leading to a chromosomally integrated HHV-6 (ciHHV-6) diagnosis. CiHHV-6 is characterized by HHV-6 DNA integration into the host genome. Accurate diagnosis relies on whole-blood quantitative PCR, distinguishing ciHHV-6 from an active infection. The neonate remained asymptomatic, and antiviral treatment was deemed unnecessary. This case underscores the importance of recognizing ciHHV-6 as a potential cause of hyperleukocytosis in neonates and highlights the value of whole-blood PCR for differentiation. Understanding the spectrum of HHV-6 infection in neonates is vital for appropriate management and prognostication.