Familial lymphohistiocytosis (FHL) is a rare, potentially fatal primary immune deficiency characterized by uncontrolled activation of the immune system. Clinical manifestations are heterogeneous, ranging from trivial infectious pictures to severe multivisceral involvement. In some cases, the picture is dominated by liver failure, making diagnosis more difficult.
An 8-month-old infant from a first-degree consanguineous marriage, born at 33 AW with an initial stay in neonatal intensive care. At 4 months of age, he presented with a prolonged fever and diarrhea, for which the mother administered an infusion of slime thistle. Clinical deterioration followed, with the appearance of pancytopenia, hepatic cytolysis, and cholestasis. The diagnosis of macrophagic activation syndrome (MAS) was made in the presence of fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis on myelogram. The immune, infectious, and metabolic workup was completed by whole-exome sequencing. The evolution was marked by neurological damage (MRI: toxic-metabolic lesions of the basal ganglia) and major hepatic cytolysis with liver failure. Treatment according to the HLH-2004 protocol was instituted, with neurological improvement but persistent hepatic damage. The whole-exome sequencing revealed a pathogenic mutation in the UNC13D gene, confirming type 3 FHL. The child is currently undergoing haplo-identical stem cell transplantation.
This case illustrates the importance of suspecting a primary immune deficiency in early-onset MAS, even in the presence of a triggering factor, such as intoxication. Hepatic involvement may dominate the picture, masking the diagnosis. In atypical forms, genetic testing is essential for appropriate curative management.
