Clinicogenetic Characterization of H Syndrome in a South African Child

ABSTRACT

H syndrome is a rare autosomal recessive genodermatosis caused by loss‐of‐function SLC29A3 variants, combining hyperpigmented indurated plaques and hypertrichosis with life‐threatening autoinflammation. We report a 5‐year‐old South African girl of first‐cousin parents who presented with hyperinflammation mimicking macrophage activation syndrome, progressing to purpura fulminans with digital gangrene and autoamputation of fingertips and toes, myocarditis, flexion contractures, flat feet, and enlarged cheeks. Next‐generation sequencing identified a homozygous SLC29A3 variant, c.7G>A (p.Val3Ile), of uncertain significance, though the phenotype fulfills published criteria. Recognizing H syndrome's cutaneous, musculoskeletal, and vascular hallmarks can shorten a potentially fatal delay in diagnosis.