Diagnostic challenges in a child with familial hemophagocytic lymphohistiocytosis type 3 (FHLH3) presenting with fulminant neurological disease.
BACKGROUND
Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessively inherited multisystem disease characterized by fever, rash, splenomegaly, cytopenias, and variable central nervous system (CNS) manifestations.


METHODS
We report the case of a 3-year-old boy who presented with splenomegaly and normocytic anemia 4 months after returning to the US from a region endemic for Leishmania infection. The child later developed progressive neurological impairment and had radiologic evidence of widespread demyelinating disease. Gene studies showed homozygosity for a mutation at Munc13-4, confirming FHLH type 3.


CONCLUSIONS
The diagnostic uncertainty that accompanies FHLH was compounded by our patient's travel history and CNS disease mimicking acute disseminated encephalomyelitis (ADEM). Diagnostic criteria for hemophagocytic lymphohistiocytosis were not consistently met, despite aggressive disease.


CONCLUSIONS
FHLH may present with fulminant demyelinating disease, mimicking ADEM, and without necessarily meeting previously defined clinical and laboratory criteria. We strongly recommend expeditious molecular testing and genetic counseling for FHLH mutations in cases of undiagnosed inflammatory CNS disease in the pediatric population.
Weisfeld-Adams
James D
JD
Department of Human Genetics and Genomic Sciences, Kravis Children's Hospital at Mount Sinai Medical Center, New York, NY 10029-6574, USA. james.weisfeld-adams@mssm.edu
Frank
Yitzchak
Y
Havalad
Vinod
V
Hojsak
Joanne M
JM
Posada
Roberto
R
Kaicker
Shipra M
SM
Wistinghausen
Birte
B
D000740:Anemia / Q000209:etiology / Q000473:pathology; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology*; D003937:Diagnosis, Differential; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D013163:Splenomegaly / Q000209:etiology / Q000473:pathology
D008565:Membrane Proteins; C507969:UNC13D protein, human