Aortic coarctation and McArdle disease in histiocytosis-lymphadenopathy plus syndrome: expanding the SLC29A3 spectrum

Abstract

Abstract Histiocytosis-lymphadenopathy plus syndrome (HLPS) is a rare inherited disorder caused by SLC29A3 variants. We report 2 Pakistani brothers with HLPS and markedly different clinical features despite identical genotypes. The 15-year-old had severe growth failure, facial dysmorphism, insulin-dependent diabetes, hypogonadotropic hypogonadism, and coarctation of the aorta (CoA) requiring balloon dilatation. Genetic testing identified SLC29A3 and PYGM variants, indicating concurrent HLPS and McArdle disease. His 20-year-old brother had insulin-dependent diabetes and celiac disease from age 3, later developing hypertension, proteinuria, and characteristic skin changes. This case highlights marked intrafamilial variability in HLPS and identifies CoA as a rare cardiovascular feature. It also supports comprehensive genetic testing in patients with early-onset diabetes and multisystem disease.