ABSTRACT
Genetic defects of SLC29A3 result in a wide range of syndromic histiocytosis that encompasses H syndrome. Patients with SLC29A3 variants typically have hyperpigmentation, hypertrichosis, hepatosplenomegaly, sensorineural hearing loss, diabetes mellitus, and hypogonadism. Herein, we identify a novel phenotype in a girl presenting with clinical and laboratory findings similar to systemic juvenile arthritis and hyperferritinemia. Exome sequencing identified a homozygous variant in SLC29A3 (NM_018344.5: c.707C>T [p.T236M]). Our patient did not show the cardinal features of the broad spectrum of SLC29A3-related disorders. She demonstrated remarkable improvement in her clinical and laboratory manifestations after starting interleukin-1 blockade (Anakinra). Recent research suggests that SLC29A3-related disorders are accompanied with autoinflammation and autoimmunity due to an overactive inflammasome pathway, which is most likely induced by mitochondrial and lysosomal dysfunction. Hence, our findings may expand the phenotypic features of the SLC29A3 variant. Patients with the SLC29A3 variant and systemic inflammation may benefit from interleukin-1 blockade as a therapeutic option.