Mutation in the SLC29A3 Gene: A New Cause of a Monogenic, Autoinflammatory Condition abstract

Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a RosaiDorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor a antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G.A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis). Pediatrics 2013;131:e1308–e1313 AUTHORS: Isabelle Melki, MD,a Karen Lambot, MD,b Laurence Jonard, PharmD, PhD,c Vincent Couloigner, MD, PhD,de Pierre Quartier, MD, PhD,aef Bénédicte Neven, MD, PhD,aefg and Brigitte Bader-Meunier, MDafg aDepartments of Pediatric Immunology, Hematology, and Rheumatology, bPediatric Radiology, and dMicrobiology, APHP, Necker Hospital, Paris, France; cDepartment of Genetics, APHP, Trousseau Hospital, Paris, France; eParis Descartes University, Sorbonne Paris Cité, Paris, France; fInstitut IMAGINE, Paris, France; and gINSERM U768, Paris, France