Hurler

Hurler syndrome, also known as mucopolysaccharidosis type I H (MPS I H), is a rare autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase (IDUA). The enzyme deficiency leads to accumulation of glycosaminoglycans dermatan sulfate and heparan sulfate in lysosomes, producing widespread cellular and organ dysfunction.

Symptoms typically appear in infancy and progress over years. Patients commonly have coarse facial features (gargoyle-like), enlarged tongue, flattened nasal bridge, and frontal bossing. Skeletal abnormalities (dysostosis multiplex) cause short stature and joint stiffness. Other features include corneal clouding, hepatosplenomegaly, hernias, recurrent respiratory infections, airway obstruction, sleep apnea, hearing loss, and valve disease. Development is usually normal at birth but deteriorates with progressive intellectual disability and motor decline if untreated.

Genetically, Hurler results from mutations in the IDUA gene, located on chromosome 4p16.3. The enzymatic deficiency disrupts breakdown of dermatan and heparan sulfate, leading to multi-systemic storage and organ damage, including central nervous system involvement in the severe form.

Diagnosis relies on clinical suspicion supported by laboratory testing. Elevated urinary glycosaminoglycans is a screening clue, with confirmation by reduced IDUA enzyme activity in leukocytes or fibroblasts and molecular genetic testing of IDUA. Prenatal testing is possible, and some regions include newborn screening.

Treatment options aim to reduce non-neurological disease and improve survival. Enzyme replacement therapy with laronidase can lessen non-neurological symptoms and improve quality of life but does not address most CNS manifestations. Hematopoietic stem cell transplantation may improve survival and cognitive outcomes when performed early, though it is not curative and carries risks. Supportive care includes respiratory support, physical therapy, and management of cardiac and orthopedic complications. Prognosis depends on severity and access to early treatment; without therapy, Hurler is typically associated with progressive disability and reduced life expectancy.