Autoimmune Encephalitis in an Infant with Biallelic AIRE Variants: Unusual Manifestation of Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1)?

Background/Purpose: A previously healthy 4-month-old boy presented with urinary retention and torticollis. Within a few days, left-sided gaze paresis and multiple cranial nerve palsies developed, leading to progressive bulbar dysfunction with dysphagia and respiratory failure despite therapy with methylprednisolone and intravenous immunoglobulins. In parallel, reduced level of consciousness and coma developed. Mucocutaneous candidiasis was also noted.

Methods: After an extensive diagnostic workup, probable seronegative autoimmune encephalitis was considered the most likely diagnosis. Plasmapheresis was performed, and consciousness and sufficient respiration were regained.

During the first 6 weeks of treatment, a steady improvement of symptoms was observed; however, during the first year of life, recurrent alternating cranial nerve palsies with accompanying somnolence occurred despite steroid pulse therapy. Due to suspected adrenal insufficiency, a permanent therapy with hydrocortisone was initiated which finally led to resolution of symptoms.

Results: Exome sequencing revealed compound-heterozygous variants in AIRE (p.Ala58Val and p.Arg257*), which, in combination, have been associated with autoimmune polyendocrinopathy syndrome type 1 (APS-1). Borderline-positive glycine receptor and APS-1-associated autoantibodies were identified in serum. Despite incomplete criteria for APS-1, this syndrome is considered likely in this patient.

Conclusion: In APS-1, autoimmune encephalitis with NMDAR or GAD autoantibodies has only been reported in three patients aged 3 months, 58 years, and 21 years. We hereby report a second infant with very early and severe neurological symptoms with glycine receptor autoantibodies. Known autoreactivity in APS-1 supports a correlation between the genetic finding and the phenotype, so that this case possibly represents an unusual manifestation of APS-1.

Publication History

Article published online:
28 October 2021