Glycogenosis type IXa (GSD IXa) manifests with short stature, hepatomegaly, elevated transaminases without hyperbilirubinemia and hypoglycemia tendency. Reports on infection susceptibility in these patients are scarce.

We report 3 family members with genetically confirmed GSD IXa who had a transient substantial hyperbilirubinemic event due to Epstein-Barr virus (EBV) hepatitis in early childhood.

Patient 1 presented at 3 years of age with icterus, leukocytosis and conjugated hyperbilirubinemia (79 mmol/l, ref. <6 mmol/l) that resolved within three months. Positive IgM serology established the EBV diagnosis. At 29 years old, he has experienced no further significant infections nor hyperbilirubinemic episodes.

Patient 2, the maternal nephew of Patient 1, presented with fever, abdominal pain, and icterus at 5 years of age. Conjugated hyperbilirubinemia (131 mmol/l) and slightly elevated CRP with lymphocytosis were observed. Positive plasma polymerase chain reaction (PCR) test and seroconversion in serial samples confirmed the EBV infection. Liver failure reached Child-Pugh class B, but the patient fully recovered without sequelae. Lymphoproliferative disease was suspected but eventually ruled out. Immunologic investigations were inconclusive. No subsequent hyperbilirubinemic nor remarkable infectious events occurred by the age of eight years.

Patient 3, the younger brother of Patient 2, experienced a conjugated hyperbilirubinemic event (107 mmol/l) at 4 years of age. Initial EBV PCR was negative. Subsequent IgG testing was positive three months later, though there were no baseline measurements during the hyperbilirubinemia. Complete recovery was achieved.

EBV appears to induce cholestatic hepatitis in GSD IXa patients. The role of potential immunodeficiency factors remains to be elucidated.