Adult presentation of histiocytosis-lymphadenopathy plus syndrome associated with hypogammaglobulinemia due to a recurrent homozygous pathogenic variant in SLC29A3: a case report

Background SLC29A3-related disorders encompass a spectrum of rare autosomal recessive conditions characterized by multisystem involvement, including immunodeficiency, lymphoproliferation, cutaneous findings, endocrine dysfunction, and growth failure. Delayed recognition is common because phenotypes are heterogeneous and overlap with more frequent disorders. Case presentation : A 33-year-old Palestinian woman born to consanguineous parents presented with lifelong recurrent severe chest infections, growth failure with short stature and microcephaly, recurrent nephrolithiasis, chronic vomiting, dysmorphic facial features, generalized hirsutism, long toes with bilateral hallux valgus, and preserved cognitive development. Laboratory evaluation revealed marked hypogammaglobulinemia, microcytic anemia, severe vitamin D deficiency with secondary hyperparathyroidism, and mildly elevated liver enzymes. Imaging demonstrated chronic small airway changes in the lungs and a right pelvi-ureteric junction stone with hydronephrosis. Whole-exome sequencing identified a homozygous pathogenic SLC29A3 variant (c.1309G > A p.Gly437Arg), confirming a genetic diagnosis of autosomal recessive histiocytosis-lymphadenopathy plus syndrome. A multidisciplinary management plan was instituted, including immunologic, pulmonary, endocrine, nephrology, and reproductive counseling pathways, with recommendations for ongoing surveillance and carrier testing. Conclusion This case highlights the value of molecular diagnosis in adults with longstanding, multisystem presentations that include immunodeficiency, growth and skeletal anomalies, endocrine abnormalities, and cutaneous features. Recognition of SLC29A3-related disease permits targeted multidisciplinary care, genetic counseling, and anticipatory surveillance for complications.