Huntsyndroom

Huntsyndroom, known in English as Hunter syndrome, is a rare X-linked lysosomal storage disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). This deficiency leads to the accumulation of glycosaminoglycans, specifically dermatan sulfate and heparan sulfate, in lysosomes and across multiple organs, producing a progressive multisystem disease.

The condition predominantly affects males; females are typically carriers and rarely show symptoms. Onset is usually in early childhood. Two main clinical forms exist: a severe form with rapid progression and cognitive decline, and a milder form with limited or no intellectual impairment. Common features include coarse facial features, hepatosplenomegaly, skeletal abnormalities (dysostosis multiplex) with joint stiffness and short stature, recurrent respiratory infections, airway obstruction, sleep apnea, and hearing loss. Corneal clouding is not typical, which helps distinguish Huntsyndroom from some other mucopolysaccharidoses.

Diagnosis is suspected from clinical findings and confirmed by laboratory tests showing low iduronate-2-sulfatase activity in leukocytes or cultured fibroblasts, and by identifying mutations in the IDS gene. Urinary glycosaminoglycans are often elevated, supporting the diagnosis.

Treatment and management focus on enzyme replacement therapy with idursulfase to reduce somatic symptoms and improve quality of life; however, it does not cross the blood-brain barrier, so cognitive decline in severe cases may continue. Hematopoietic stem cell transplantation has been attempted in some cases with variable outcomes. Supportive care includes airway management, physical therapy, regular monitoring of hearing, vision, and skeletal health, and multidisciplinary follow-up.

Epidemiology indicates a very rare incidence, approximately 1 in 100,000 to 1 in 170,000 male births. Prognosis varies by form, with severe disease associated with reduced lifespan and milder disease allowing longer survival.