Introduction
UNC80 deficiency is an ultra-rare autosomal recessive condition that has been reported in less than 50 patients to date. The objective of this study is to present the first reported case of infantile spasms in a child with UNC80 deficiency and to describe atypical reactions to conventional treatments for IS.

Case Presentation
A four-month-old female presented to the emergency department for paroxysmal spells overnight, occurring in clusters and characterized by fixed upward gaze, sudden arm movements, and slow nodding of the head. The patient's past medical history at the time of presentation was significant for poor feeding, torticollis, and hypotonia.

Diagnostic Workup
Upon initial presentation, EEG was obtained, which showed hypsarrhythmia consistent with infantile spasms; lumbar puncture was performed but was unremarkable. Soon after, exome sequencing revealed a homozygous pathogenic variant (c.8574+ T>C) in UNC80. MRI was later obtained, which was grossly normal.

Treatment and Management
During her initial hospital admission, clobazam and levetiracetam were started. ACTH therapy was started but was discontinued due to adverse events. As an outpatient, she was prescribed vigabatrin; however, due to side effects and poor clinical response, it was discontinued. She then started valproate and zonisamide. After transitioning to a new hospital, ACTH therapy was reattempted and clobazam was increased.

Outcome and Follow-Up
At the initial presentation, within 24 hours of initiating ACTH therapy, the patient became febrile and severely hyperglycemic. Upon termination of ACTH, glucose levels returned to normal, and her condition stabilized. Vigabatrin therapy resulted in initial clinical improvement, but the patient could no longer perform tasks they once could, such as bringing hands to midline and guiding things to their mouth. After a short period on vigabatrin, the patient became increasingly sedated with worsening spasms. Vigabatrin was discontinued, leading to improvement in sedation and functioning within days. The subsequent addition of valproate and zonisamide did not stop the spasms.



The patient was transferred to a new hospital and ACTH was reinitiated, resulting in moderate resolution of symptoms, although recurrence of spasms while weaning was observed. Notably, the initial side effects of hyperglycemia and fever were not observed. High-dose ACTH was administered for an additional week, after which the patient became free from spasms.

Discussion
Based on our literature review, this represents the first described case of infantile spasms in a patient with UNC80 deficiency. The significant hyperglycemic response to the initial ACTH therapy may have been secondary to chronic malnutrition, as she had poor oral intake at that time. The second trial occurred in a state of improved nutrition, highlighting the potential importance of adequate caloric intake when initiating ACTH therapy. The patient’s poor response to vigabatrin is notable.

Conclusion
UNC80 deficiency is an ultra-rare condition that may be associated with an increased risk for infantile spasms. Given this patient’s atypical clinical course and response to medications, it will be important to monitor and describe medication reactions in other patients with UNC80 deficiency.