Emergence and compartmentalization of fatal multi-drug-resistant cytomegalovirus infection in a patient with autosomal-recessive severe combined immune deficiency

J Pediatr Hematol Oncol. 2004 Sep;26(9):601-5. doi: 10.1097/01.mph.0000135283.77668.6a.

Abstract

The authors describe a patient with autosomal-recessive severe combined immunodeficiency (SCID) with severe, multiorgan cytomegalovirus (CMV) disease. In the face of appropriate therapy, the patient developed a 100-fold gradient in viral load across the blood-brain barrier. Disseminated disease, including pneumonitis, contributed to a fatal outcome. Serial genotypic analyses revealed multiple UL97 and UL54 (DNA polymerase) mutations that conferred phenotypic resistance to all currently licensed systemic CMV antivirals.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Cell Compartmentation
  • Chromosome Aberrations
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / virology*
  • DNA, Viral / analysis
  • DNA-Directed DNA Polymerase / genetics
  • Drug Resistance, Multiple, Viral*
  • Fatal Outcome
  • Genes, Recessive
  • Humans
  • Infant
  • Male
  • Mutation / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Polymerase Chain Reaction
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / virology*
  • Viral Load
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • DNA, Viral
  • UL54 protein, Human herpesvirus 5
  • Viral Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • ganciclovir kinase
  • DNA-Directed DNA Polymerase