AIRE Gene Mutation Presenting at Age 2 Years With Autoimmune Retinopathy and Steroid-Responsive Acute Liver Failure: A Case Report and Literature Review

• Published in: Frontiers in immunology 2021-05, Vol.12, p.687280
• Main Authors: Sakaguchi, Hirotaka, Mizuochi, Tatsuki, Haruta, Masatoshi, Takase, Ryuta, Yoshida, Shigeo, Yamashita, Yushiro, Nishikomori, Ryuta
• Format: Article
• Language: English
• Subjects: acute liver failure; Administration, Intravenous; Adrenal Cortex Hormones - administration & dosage; AIRE; AIRE Protein; Autoantibodies - blood; Autoimmune Diseases - diagnosis; Autoimmune Diseases - drug therapy; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; autoimmune hepatitis; Azathioprine - administration & dosage; Child, Preschool; children; corticosteroid; Drug Therapy, Combination; Female; Genetic Predisposition to Disease; Humans; Immunology; Immunosuppressive Agents - administration & dosage; Liver Failure, Acute - diagnosis; Liver Failure, Acute - drug therapy; Liver Failure, Acute - genetics; Liver Failure, Acute - immunology; Methylprednisolone - administration & dosage; Mutation; Phenotype; Polyendocrinopathies, Autoimmune - diagnosis; Polyendocrinopathies, Autoimmune - drug therapy; Polyendocrinopathies, Autoimmune - genetics; Polyendocrinopathies, Autoimmune - immunology; Pulse Therapy, Drug; Recoverin - immunology; Retinal Diseases - diagnosis; Retinal Diseases - drug therapy; Retinal Diseases - genetics; Retinal Diseases - immunology; Transcription Factors - genetics; Treatment Outcome
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.687280

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic autosomal recessive disorder caused by mutation in the autoimmune regulator (AIRE) gene. Patients usually are diagnosed at ages between 5 and 15 years when they show 3 or more manifestations, most typically mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. APECED-associated hepatitis (APAH) develops in only 10% to 40% of patients, with severity varying from subclinical chronic active hepatitis to potentially fatal acute liver failure (ALF). Ocular abnormalities are fairly common, most often keratopathy but sometimes retinopathy. Here we report a 2-year-old Japanese girl with an gene mutation who developed APAH with ALF, preceded by autoimmune retinopathy associated with anti-recoverin antibody before major symptoms suggested a diagnosis of APECED. Intravenous pulse methylprednisolone therapy followed by a corticosteroid combined with azathioprine treatment resolved ALF and achieved control of APAH. To our knowledge, our patient is the youngest reported to have ALF resulting from an gene mutation. Pulse methylprednisolone induction therapy followed by treatment with corticosteroid plus azathioprine may well be effective in other children with APAH and gene mutations.