H syndrome is a very rare genetic syndrome involving multiple systems, with approximately 100 cases reported to date. It is caused by mutations in the SLC29A3 gene on chromosome 10q22 that codes for human equilibrative nucleoside transporter 3 (hENT3) and is inherited in an autosomal recessive pattern.

H syndrome is characterized by a variable range of clinical features, most of which start with the letter "H," including cutaneous hyperpigmentation, hypertrichosis, heart anomalies, hematologic abnormalities, hyperglycemia, hepatosplenomegaly, hearing loss, short stature (low height), and hallux valgus.

The disease presents in the first months of life through early adulthood. Symmetrical cutaneous hyperpigmentation of the inner thighs, with accompanying hypertrichosis and sclerodermatous thickening, is the most common feature of the disease. Pericarditis is the most common cardiac manifestation of the syndrome. Hematologic abnormalities range from a microcytic anemia to pancytopenia, red cell aplasia, and myelofibrosis. Hyperglycemia and consequent insulin-dependent diabetes mellitus in patients with H syndrome is thought to be due to pancreatic exocrine insufficiency.

Other findings in H syndrome include recurrent febrile episodes, agenesis of the inferior vena cava with varicose veins, proptosis or exophthalmos, hypogonadism, chronic diarrhea, inflammatory arthritis, and generalized lymphadenopathy. Laboratory results often reveal chronic elevation of inflammatory markers.