Hurler's Syndrome

Synonym: Mucopolysaccharidosis Type IH

The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes including Hurler (severe), Scheie (mild) and Hurler-Scheie (intermediate) syndromes.¹

• The incidence has been estimated at 1 in 75,000.²
• The mode of inheritance is autosomal recessive.

Affected children appear normal at birth but usually develop the characteristic appearance within the first year of life.

• Mental retardation: maximum functional development is reached when the child is aged between 2 and 4 years³
• Short stature
• Coarse facies and enlarged tongue
• Corneal clouding
• Hearing impairment
• Umbilical and inguinal hernias
• Joint stiffness and skeletal deformities
• Cardiomyopathy and coronary heart disease
• Hepatosplenomegaly
• Dysostosis multiplex: enlarged skull, enlarged but shortened bones, malformed pelvis and other skeletal defects

• Other mucopolysaccharidoses: Hunter syndrome (Mucopolysaccharidosis Type II) has no corneal clouding and progression is slower.
• Other causes of mental retardation and short stature.

• Urine: raised levels of dermatan sulphate and heparan sulphate are found in patients with mucopolysaccharidoses.
• Definitive diagnosis is established by alpha-L-iduronidase enzyme assay using artificial substrates in cultured fibroblasts or isolated leukocytes.
• Carrier testing can be performed by differentiating normal enzyme activity from half-normal levels of enzyme activity.
• Prenatal diagnosis: using cultured amniotic fluid cells or chorionic villus biopsies.
• Molecular diagnosis: difficult because of genetic heterogeneity.
• Assessment of complications will include an echocardiogram and MRI brain scan.

• Palliative treatment includes the provision of multidisciplinary treatment and support for affected children and their families.
• Orthopaedic surgery for joint contractures and skeletal deformities.
• Corneal transplants may be required.
• Enzyme replacement: laronidase is licensed for long-term replacement therapy in the treatment of non-neurological manifestations of Hurler's syndrome; it may reduce the excess carbohydrates stored in organs and lead to some functional improvements.
• Allogenic marrow transplant and gene therapy may present treatment possibilities in the future.

• Orthopaedic complications lead to pain and immobility.
• Upper airways obstruction.
• Increased susceptibility to infections of the respiratory tract.

• Death usually occurs by the age of 14 years.
• Common causes of death include upper airways obstruction, cardiac insufficiency and respiratory tract infections.