Gestational alloimmune liver disease (GALD) is a rare neonatal disorder with high mortality and morbidity. The patients come to caregivers' attention aged a few hours or days. The disease manifests as acute liver failure with or without siderosis. The differential diagnosis of neonatal acute liver failure (NALF) is broad, including mainly immunologic, infectious, metabolic and toxic disorders. The most common cause, however, is GALD followed by herpes simplex virus (HSV) infection. The best suited pathophysiological paradigm of GALD is that of a maternofetal alloimmune disorder. State of the art treatment combines intravenously administered immunoglobulin (IVIG) with exchange transfusion (ET). We report an infant born at 35 + 2 weeks' gestation in whom GALD had a favorable course, of interest because premature birth in our patient may have exerted protective aspects and lessened morbidity in that intrauterine exposure to maternal complement-fixing antibodies was shortened. The diagnosis of GALD was challenging and difficult. We suggest a modified diagnostic algorithm combining clinical findings with histopathologic findings in liver and lip mucosa and, if available, on abdominal magnetic resonance imaging-study focusing on the liver, spleen, and pancreas. This diagnostic workup must be followed by ET and subsequent administration of IVIG without delay
