PEDIATRIC LEIGH SYNDROME: EVIDENCE OF IMMUNE DYSFUNCTION AND SUCCESSFUL TREATMENT WITH IMMUNOGLOBULIN REPLACEMENT

Abstract

<h3>Introduction</h3> Leigh syndrome (LS) is a heterogenous, progressive neurodegenerative mitochondrial disorder (MD). Genetic mutations of electron transport chain complex subunits result in defective oxidative phosphorylation and impaired ATP production. Energy deprivation during periods of increased energy consumption (e.g. illness, infection) can trigger disease progression and death. Recent work recognizes immunodeficiency as a new phenotype of MD. Immune dysfunction has not been established as a clinical feature of LS. We propose LS features immune dysfunction with clinical response to immunoglobulin replacement through a case series of six LS patients with recurrent SIRS/infections and complete immunologic phenotyping. <h3>Case Description</h3> Our case series includes six patients (9-17yo) with early onset LS. Symptoms developed 3d-12mo of life – developmental delay, hypotonia, feeding difficulties, multisystemic effects. Patients presented to a tertiary academic medical center with recurrent infections including viral airway infections, RSV bronchiolitis, otitis media, and sepsis. An immunologic workup was notable for deficient vaccine response to polysaccharide antigens, decreased class-switched B cells and memory T cells (CD45RO⁺) in all 6 patients. Immunoglobulin therapy was initiated – after replacement, 4 out of 6 patients experienced decreased infections (hospitalizations/year reduced by 53-89%). <h3>Discussion</h3> Immunodeficiency is a feature of LS. Our case series demonstrated clinical and laboratory evidence of immune dysfunction with specific antibody deficiency phenotype and low class-switched B cells & memory T cells. Evaluation should include complete immunologic workup. LS survival is poor – infection is a main cause of death in ∼20% LS patients. Immunoglobulin replacement in LS may improve outcomes and decrease morbidity/mortality.