Neonatal Onset of Hemophagocytic Lymphohistiocytosis Due to Prenatal Varicella-Zoster Infection in a Neonate with Griscelli Syndrome Type 2

Abstract

Griscelli syndrome (GS) type 2 is an inborn error of the immune system classified as immune dysregulation. This autosomal recessive disease has three types with different genetic causes. In all variants, hypopigmentation is common, but neurological involvement or immunodeficiency varies in severity. The known genetic defects associated with GS include mutations in myosin 5 A (GS type1), guanosine triphosphate binding protein (GS type 2), and human melanophilin (GS type 3). Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition and is characterized by severe, ineffective, and uncontrolled inflammatory reactions. A HLH can be classified as primary or secondary, with secondary resulting from autoimmunity, malignancy, spontaneous or infectious causes. Many prenatal infections can cause long-term complications in the fetus, including toxoplasmosis, rubella, cytomegalovirus, herpes simplex, syphilis, parvovirus, and varicella zoster (known as TORCH syndrome). Prenatal infections have been associated with TORCH for a long time, but HLH is a rare complication. The report presents a case of HLH with symptoms of sepsis, organomegaly, and cytopenia from the time of birth. A genetic test confirmed Griscelli Syndrome Type 2, which was diagnosed during an immunologic consultation regarding partial albinism not seen in family members. Prenatal infection was the only approved finding in the investigation into the trigger of HLH in this patient starting in the first days of life. Accordingly, the patient was diagnosed with type 2GS syndrome with neonatal-onset HLH caused by a prenatal infection.

Macrophage Activation Syndrome in Viral Sepsis

“…Lastly, there are few reported cases of varicella-zoster virus (VZV) infection as a trigger of HLH, primarily in the pediatric population. However, some cases have been associated with underlying immune system disorders, such as adenosine deaminase 2 (ADA2) deficiency or Griscelli syndrome [79][80][81][82].…”