*Purpose: The AIRE gene plays an important role in immune tolerance by driving negative selection of self-recognizing T-cells. Mutations in this gene are responsible for Autoimmune Polyglandular Syndrome type 1, an autosomal recessive condition characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. This condition is extremely rare and only affects 1 in 2 to 3 million newborns. Hepatic manifestations are seen in 10-20% of patients and include autoimmune hepatitis and chronic active hepatitis, however fulminant hepatitis has only been reported in a few patients.

*Methods: A 17 month-old male presented to our facility with acute liver failure. He was healthy aside from episodes of transient urticarial rash, oral thrush, and recurrent diaper rash after his first birthday. His newborn state screen was normal. There were no reported drug ingestions or toxin exposures. His family history was unremarkable and there was no consanguinity. He had developed a viral illness one week previously, and was noted to have jaundice two days prior to admission. On initial presentation, he had AST 2882 U/L, ALT 2317 U/L, bilirubin 7.5 mg/dL (direct bilirubin 4.4 mg/dL), and INR 2.7. His physical exam was significant for jaundice but he had no hepatosplenomegaly.

Fatty acid oxidation disorder was considered due to initial episodes of hypoglycemia which subsequently resolved with dextrose 10%. His clinical status deteriorated within 48 hours of admission with worsening coagulopathy despite vitamin K administration and suggestion of early hepatic encephalopathy. Metabolic testing did not reveal a unifying diagnosis. Positive smooth muscle antibodies with 1:40 titers raised concern for autoimmune hepatitis and he was started on intravenous steroids. His respiratory viral panel was positive for Respiratory Syncytial Virus but all other infectious workup came back negative. As his workup failed to reveal a particular cause, the etiology of his liver failure was felt to be likely post-infectious or autoimmune.

*Results: He successfully underwent living related donor transplantation on day 5 of admission, and liver pathology showed extensive parenchymal extinction with bile ductular reaction but no specific diagnosis. During his pre-transplant workup, rapid whole-exome sequencing revealed compound heterozygous, pathogenic variants in the AIRE gene. The maternal variant showed c.769C>T (p.R257X), and the paternal variant showed c.1095+1G>A in exon 9 (affects splicing).

*Conclusions: This case is the first pediatric patient with AIRE mutation to have fulminant hepatic failure as the initial presentation requiring liver transplantation. This highlights the importance of considering rapid whole-exome sequencing in young children with fulminant hepatic failure with no obvious cause.

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