The underlying mechanism is a deficiency of alpha-L iduronidase, an enzyme responsible for breaking down GAGs.

[citation needed] One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3–6 months of age.

Patients may experience debilitating spine and hip deformities, carpal tunnel syndrome, and joint stiffness.

[4][5] Children with Hurler syndrome carry two defective copies of the IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4.

[6] Because Hurler syndrome is an autosomal recessive disorder, affected persons have two nonworking copies of the gene.

The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease.

Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder.

Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.

[5] Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) can be used as treatments for MPS I. BMT from siblings with identical HLA genes and from relatives with similar HLA genes can significantly improve survival, cognitive function, and physical symptoms.

In these cases, UCBT from unrelated donors can increase survival, decrease physical signs of the disease, and improve cognition.

[10] A British study from 2008 found a median estimated life expectancy of 8.7 years for patients with Hurler syndrome.

Patients who did not receive bone marrow transplants had a significantly reduced lifespan, with a median age of 6.8 years.

In animal models, delivery of the iduronidase gene has been accomplished with retrovirus, adenovirus, adeno-associated virus, and plasmid vectors.

Gene therapy has improved survival, neurological, and physical symptoms; however, some animals have developed unexplained liver tumors.

If safety issues can be resolved, gene therapy may provide an alternative human treatment for MPS disorders in the future.

[11] Sangamo Therapeutics, headquartered in Richmond, California, is currently conducting a clinical trial involving gene editing using zinc finger nuclease (ZFN) for the treatment of MPS I.

[12] In 1919, Gertrud Hurler, a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation.