Hurler syndrome was first described by German pediatrician, Gertrud Hurler in 1919. It is one of the 11 disorders of the mucopolysaccharidoses (MPS). Hurler syndrome is considered as mucopolysaccharidosis type I (MPH I) and formerly known as gargoylism. In 1962, a milder form of MPS I was identified and named as Scheie syndrome.
It is an inherited lysosomal disorder caused by the absence of alpha-L-iduronidase enzyme which responsible for degradation of glycosaminoglycans (GAG or mucopolysaccharides). This leads to a buildup of dermatan sulfate and heparin sulfate in multiple tissues, resulting in progressive deterioration and, eventually, death.
Hurler syndrome is an autosomal recessive disorder due to a defective gene which encodes for the enzyme alpha-L-iduronidase (IUDA) that is located on chromosome 4.
The incidence of Hurler syndrome is approximately 1 in 100,000 births. Male and female children are equally affected. All races and ethnicities are at risk of inheriting the disease.
Hurler syndrome is caused by a deficiency of a lysosomal enzyme, IUDA, which aids in the breakdown of dermatan sulfate and heparin sulfate (GAG). This finally results in the accumulation of large amounts of GAG in the body, eventually causing the cells to become severely dysfunctional leading to death. The deposition of GAG causes enlargement and thickening of various organs like the heart, spleen, liver, muscles, connective tissues, joints, and the central nervous system causing severe functional impairment.
Hurler Syndrome is considered as MPS I. The presentation and course of the disease vary due to underlying IUDA mutations and a consequent residual degree of enzyme activity. MPS I is further subdivided into three subtypes.
Children with Hurler syndrome are usually not born with signs but develop symptoms during the first year of life. Developmental delay may become apparent by the age of 1 to 2 years, with a maximum functional age of 2 to 4 years. The average age of mortality is 5 years, and nearly all patients die before 10 years of age.
Most therapies for Hurler syndrome are directed towards treatment of complications and are not specific for an underlying abnormality.
The life expectancy of MPS with a median age is 8.7 years. The survival rate is varied based on bone marrow transplantation. Patients who received successful bone marrow transplantation had a 2-year survival rate of 68% and 10-year survival rate of 64% when compared to those individuals who did not receive the transplants. They had a significantly decreased life expectancy, with the median age of 6.8 years.
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