To report on a newborn infant with a homozygous mutation in the ACP5 gene associated with a type-1 interferonopathy, workup for possible mimics, and initiation of potentially disease-modifying immunotherapy.
Variations in the ACP5 gene causes Spondyloenchondrodysplasia with immunodeficiency (SPENCDI), a type I interferonopathy leading to multiorgan autoimmune sequalae due to increased interferon activity. The CNS is particularly susceptible resulting in developmental delay, intracranial calcification, white matter disease, atrophy, and spasticity. Herein we describe a newborn with a complex hematologic and immunologic presentation, and discuss mimics and differential diagnoses for type I interferonopathies.
Retrospective chart review.
Petechiae on the face and trunk was noted at birth on a full-term infant boy born to consanguineous Afghani parents who previously had an infant and toddler die from unknown causes. Within 3 hours, the infant manifested full body petechiae and tachypnea.
He underwent workup for familial hemophagocytic lymphohistiocytosis (due to high ferritin, D-dimer, LDH, among other abnormalities) and X-linked adrenoleukodystrophy (newborn screens indicated elevated very long chain fatty acids). Signal prolongation was observed on brain MRI within subcortical and deep white matter.
On DOL 20 he was started on steroids with improvement in laboratory abnormalities but had rising liver enzymes with attempted wean of steroids. On DOL 54, trio whole exome sequencing indicated a homozygous mutation in the ACP5 gene concerning for SPENCDI, inherited from each parent. He was started on a JAK2 inhibitor, baricitinib, on DOL 68, discharged on DOL 137, meeting developmental milestones at follow up on DOL 167.Presentation at birth of SPENCDI is extremely rare with only one other reported case of neonatal thrombocytopenia. As new therapies emerge with potential to impact disease course, genetic testing is indispensable. The impact of JAK2 inhibitors on preventing CNS injury and improving neurodevelopmental outcomes in type 1 interferonopathies remains to be determined.