Hurler syndrome is caused by a genetic mutation that affects the body’s ability to produce a specific enzyme called alpha-L-iduronidase. This enzyme is crucial for breaking down certain complex sugar molecules known as glycosaminoglycans (GAGs), which are long chains of sugar molecules found throughout the body, especially in connective tissues. When the alpha-L-iduronidase enzyme is missing or deficient due to the mutation, these sugar molecules accumulate inside cells, particularly within lysosomes—the cell’s recycling centers—leading to progressive damage in various tissues and organs.
The root cause lies in mutations in the IDUA gene, which provides the instructions for making the alpha-L-iduronidase enzyme. These mutations disrupt the normal production or function of the enzyme, resulting in its deficiency or complete absence. Without enough functional enzyme, the body cannot properly break down and recycle GAGs, causing them to build up in cells and tissues. This buildup interferes with normal cellular function and leads to the symptoms and complications associated with Hurler syndrome.
Hurler syndrome is inherited in an autosomal recessive pattern. This means that a child must inherit two copies of the mutated IDUA gene—one from each parent—to develop the condition. Parents who carry only one mutated copy typically do not show symptoms but are carriers who can pass the gene to their children. If both parents are carriers, there is a 25% chance with each pregnancy that the child will have Hurler syndrome.
The accumulation of GAGs due to enzyme deficiency affects multiple body systems. It leads to abnormal development and function of connective tissues, bones, heart, respiratory system, and the nervous system. This widespread impact explains the range of symptoms seen in Hurler syndrome, such as skeletal deformities, heart valve problems, enlarged liver and spleen, respiratory difficulties, and developmental delays.
In summary, Hurler syndrome is caused by inherited mutations in the IDUA gene that result in a deficiency of the alpha-L-iduronidase enzyme. This enzyme deficiency prevents the breakdown of glycosaminoglycans, causing their accumulation and leading to progressive damage in many tissues and organs throughout the body. The genetic nature and enzyme deficiency are central to understanding the disease’s cause and its effects on the body.
