The EIF2B1 gene is a protein coding gene which has been implicated in pathways for insulin translation and the cellular stress response. Previously described patients with novel EIF2B1 heterozygous variants presented with neonatal onset diabetes and transient liver dysfunction. Rarely it can result into fatal acute liver failure. We describe a rare case of a 2 year old male with a known heterozygous missense variant in EIF2B1 (NM_001414.3: c.131G>A; p.(Gly44Asp)). Location: GRCh37 (hg19) – Chr12:g.124115065) who presented with recurrent fulminant liver failure which unfortunately was fatal.

This patient was born at term (39 weeks) with no dysmorphic features to non-consanguineous parents. At 2 months old he presented neonatal diabetes and liver dysfunction (ALT 1907) which recovered.

At 2.5 years old, he presented with fever and vomiting and was discharged home. He presented two days later with hypoglycaemia, acute liver failure and renal impairment. He was transferred to intensive care with INR 5.6, ALT 956 and lactate 3.5. His illness progressed to multiorgan failure making him unsuitable for liver transplantation.

Over three months he recovered from acute liver failure with supportive treatment (ALT 52, INR 1.2). CT head confirmed a severe hypoxic cerebral insult needing intensive neuro rehabilitation. In hospital he developed a further episode of acute liver failure after three months (ALT 700, INR 3.5) with a rapid deterioration in intensive care which proved fatal.

This case highlights the spectrum of presentation of EIF2B1 variants. Parents need to be counselled about risk of recurrent acute liver failure with subsequent fatality.