Adult presentation of SLC29A3-related disorder spectrum with marked hypogammaglobulinemia due to a recurrent homozygous pathogenic variant (G437R): a case report

Abstract

SLC29A3-related disorder spectrum encompasses rare autosomal recessive conditions characterized by multisystem involvement, including immunodeficiency, lymphoproliferation, cutaneous findings, endocrine dysfunction, and growth failure. The clinical presentation is highly heterogeneous, often leading to delayed diagnosis, particularly in adults. A 33-year-old Palestinian woman born to consanguineous parents presented with a lifelong history of recurrent severe respiratory infections, growth failure (short stature and microcephaly), recurrent nephrolithiasis, chronic vomiting, generalized hirsutism, and bilateral hallux valgus. Laboratory evaluation revealed marked hypogammaglobulinemia (IgG <320 mg/dL, IgA <25 mg/dL, IgM <25 mg/dL), microcytic anemia, and severe vitamin D deficiency. Imaging confirmed chronic pulmonary small-airway changes and a chronically small right kidney with recurrent stones. Whole-exome sequencing identified a homozygous pathogenic SLC29A3 variant (c.1309G>A; p.Gly437Arg), establishing a diagnosis within the SLC29A3-related disorder spectrum. This case is unique due to its adult presentation, the exceptional severity of the humoral immunodeficiency, and the associated renal manifestations, which are infrequently reported in this spectrum. This report underscores the importance of considering SLC29A3-related disorder spectrum in adults with multisystem disease. Recognition of this spectrum enables targeted multidisciplinary care, including immunoglobulin replacement therapy and anticipatory surveillance for endocrine and renal complications.